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Published in: Journal of Hematology & Oncology 1/2014

Open Access 01-12-2014 | Review

Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction- a novel mechanism for maintaining vascular function

Authors: Ying Shao, Zhongjian Cheng, Xinyuan Li, Valeria Chernaya, Hong Wang, Xiao-feng Yang

Published in: Journal of Hematology & Oncology | Issue 1/2014

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Abstract

Endothelial dysfunction is a pathological status of the vascular system, which can be broadly defined as an imbalance between endothelium-dependent vasoconstriction and vasodilation. Endothelial dysfunction is a key event in the progression of many pathological processes including atherosclerosis, type II diabetes and hypertension. Previous reports have demonstrated that pro-inflammatory/immunoeffector cytokines significantly promote endothelial dysfunction while numerous novel anti-inflammatory/immunosuppressive cytokines have recently been identified such as interleukin (IL)-35. However, the effects of anti-inflammatory cytokines on endothelial dysfunction have received much less attention. In this analytical review, we focus on the recent progress attained in characterizing the direct and indirect effects of anti-inflammatory/immunosuppressive cytokines in the inhibition of endothelial dysfunction. Our analyses are not only limited to the importance of endothelial dysfunction in cardiovascular disease progression, but also expand into the molecular mechanisms and pathways underlying the inhibition of endothelial dysfunction by anti-inflammatory/immunosuppressive cytokines. Our review suggests that anti-inflammatory/immunosuppressive cytokines serve as novel therapeutic targets for inhibiting endothelial dysfunction, vascular inflammation and cardio- and cerebro-vascular diseases.
Appendix
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Literature
2.
go back to reference Aird WC: Endothelium as an organ system. Crit Care Med. 2004, 32 (5 Suppl): S271-S279.PubMed Aird WC: Endothelium as an organ system. Crit Care Med. 2004, 32 (5 Suppl): S271-S279.PubMed
3.
go back to reference Jaffe EA: Cell biology of endothelial cells. Hum Pathol. 1987, 18 (3): 234-239.PubMed Jaffe EA: Cell biology of endothelial cells. Hum Pathol. 1987, 18 (3): 234-239.PubMed
4.
go back to reference Mai J, Virtue A, Shen J, Wang H, Yang XF: An evolving new paradigm: endothelial cells–conditional innate immune cells. J Hematol Oncol. 2013, 6: 61-PubMedCentralPubMed Mai J, Virtue A, Shen J, Wang H, Yang XF: An evolving new paradigm: endothelial cells–conditional innate immune cells. J Hematol Oncol. 2013, 6: 61-PubMedCentralPubMed
5.
go back to reference Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ: Endothelial function and dysfunction. Part I: methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005, 23 (1): 7-17.PubMed Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ: Endothelial function and dysfunction. Part I: methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005, 23 (1): 7-17.PubMed
6.
go back to reference Yang XF, Yin Y, Wang H: Vascular inflammation and atherogenesis are activated via receptors for pamps and suppressed by regulatory t cells. Drug Discov Today Ther Strateg. 2008, 5 (2): 125-142.PubMedCentralPubMed Yang XF, Yin Y, Wang H: Vascular inflammation and atherogenesis are activated via receptors for pamps and suppressed by regulatory t cells. Drug Discov Today Ther Strateg. 2008, 5 (2): 125-142.PubMedCentralPubMed
7.
go back to reference Boisrame-Helms J, Kremer H, Schini-Kerth V, Meziani F: Endothelial dysfunction in sepsis. Curr Vasc Pharmacol. 2013, 11 (2): 150-160.PubMed Boisrame-Helms J, Kremer H, Schini-Kerth V, Meziani F: Endothelial dysfunction in sepsis. Curr Vasc Pharmacol. 2013, 11 (2): 150-160.PubMed
8.
go back to reference Hansell C, Nibbs R: Professional and part-time chemokine decoys in the resolution of inflammation. Sci STKE. 2007, 2007 (384): e18- Hansell C, Nibbs R: Professional and part-time chemokine decoys in the resolution of inflammation. Sci STKE. 2007, 2007 (384): e18-
9.
go back to reference Trayhurn P, Wood IS: Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans. 2005, 33 (Pt 5): 1078-1081.PubMed Trayhurn P, Wood IS: Signalling role of adipose tissue: adipokines and inflammation in obesity. Biochem Soc Trans. 2005, 33 (Pt 5): 1078-1081.PubMed
10.
go back to reference Pedersen BK, Febbraio MA: Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012, 8 (8): 457-465.PubMed Pedersen BK, Febbraio MA: Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012, 8 (8): 457-465.PubMed
11.
go back to reference Miller YI, Choi SH, Wiesner P, Fang L, Harkewicz R, Hartvigsen K, Boullier A, Gonen A, Diehl CJ, Que X, Montano E, Shaw PX, Tsimikas S, Binder CJ, Witztum JL: Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ Res. 2011, 108 (2): 235-248.PubMedCentralPubMed Miller YI, Choi SH, Wiesner P, Fang L, Harkewicz R, Hartvigsen K, Boullier A, Gonen A, Diehl CJ, Que X, Montano E, Shaw PX, Tsimikas S, Binder CJ, Witztum JL: Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ Res. 2011, 108 (2): 235-248.PubMedCentralPubMed
12.
go back to reference Jialal I, Kaur H, Devaraj S: Toll-like receptor status in obesity and metabolic syndrome: a translational perspective. J Clin Endocrinol Metab. 2014, 99 (1): 39-48.PubMed Jialal I, Kaur H, Devaraj S: Toll-like receptor status in obesity and metabolic syndrome: a translational perspective. J Clin Endocrinol Metab. 2014, 99 (1): 39-48.PubMed
13.
go back to reference Lackie JM: A Dictionary of Biomedicine. 2010, Oxford University Press, Oxford Lackie JM: A Dictionary of Biomedicine. 2010, Oxford University Press, Oxford
14.
go back to reference Munoz C, Carlet J, Fitting C, Misset B, Bleriot JP, Cavaillon JM: Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest. 1991, 88 (5): 1747-1754.PubMedCentralPubMed Munoz C, Carlet J, Fitting C, Misset B, Bleriot JP, Cavaillon JM: Dysregulation of in vitro cytokine production by monocytes during sepsis. J Clin Invest. 1991, 88 (5): 1747-1754.PubMedCentralPubMed
15.
go back to reference Kasai T, Inada K, Takakuwa T, Yamada Y, Inoue Y, Shimamura T, Taniguchi S, Sato S, Wakabayashi G, Endo S: Anti-inflammatory cytokine levels in patients with septic shock. Res Commun Mol Pathol Pharmacol. 1997, 98 (1): 34-42.PubMed Kasai T, Inada K, Takakuwa T, Yamada Y, Inoue Y, Shimamura T, Taniguchi S, Sato S, Wakabayashi G, Endo S: Anti-inflammatory cytokine levels in patients with septic shock. Res Commun Mol Pathol Pharmacol. 1997, 98 (1): 34-42.PubMed
16.
go back to reference Murdaca G, Spano F, Cagnati P, Puppo F: Free radicals and endothelial dysfunction: potential positive effects of TNF-alpha inhibitors. Redox Rep. 2013, 18 (3): 95-99.PubMed Murdaca G, Spano F, Cagnati P, Puppo F: Free radicals and endothelial dysfunction: potential positive effects of TNF-alpha inhibitors. Redox Rep. 2013, 18 (3): 95-99.PubMed
17.
go back to reference Kusuhara M, Isoda K, Ohsuzu F: Interleukin-1 and occlusive arterial diseases. Cardiovasc Hematol Agents Med Chem. 2006, 4 (3): 229-235.PubMed Kusuhara M, Isoda K, Ohsuzu F: Interleukin-1 and occlusive arterial diseases. Cardiovasc Hematol Agents Med Chem. 2006, 4 (3): 229-235.PubMed
18.
go back to reference Aroor AR, McKarns S, Demarco VG, Jia G, Sowers JR: Maladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance. Metabolism. 2013, 62 (11): 1543-1552.PubMed Aroor AR, McKarns S, Demarco VG, Jia G, Sowers JR: Maladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance. Metabolism. 2013, 62 (11): 1543-1552.PubMed
19.
go back to reference Deanfield JE, Halcox JP, Rabelink TJ: Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007, 115 (10): 1285-1295.PubMed Deanfield JE, Halcox JP, Rabelink TJ: Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007, 115 (10): 1285-1295.PubMed
20.
go back to reference Pober JS, Sessa WC: Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 2007, 7 (10): 803-815.PubMed Pober JS, Sessa WC: Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 2007, 7 (10): 803-815.PubMed
21.
go back to reference Bautista LE: Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence. J Hum Hypertens. 2003, 17 (4): 223-230.PubMed Bautista LE: Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence. J Hum Hypertens. 2003, 17 (4): 223-230.PubMed
22.
go back to reference Hadi HA, Carr CS, Al Suwaidi J: Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag. 2005, 1 (3): 183-198.PubMedCentralPubMed Hadi HA, Carr CS, Al Suwaidi J: Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag. 2005, 1 (3): 183-198.PubMedCentralPubMed
23.
go back to reference van den Oever IA, Raterman HG, Nurmohamed MT, Simsek S: Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus. Mediators Inflamm. 2010, 2010: 792393-PubMedCentralPubMed van den Oever IA, Raterman HG, Nurmohamed MT, Simsek S: Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus. Mediators Inflamm. 2010, 2010: 792393-PubMedCentralPubMed
24.
go back to reference Cai H, Harrison DG: Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000, 87 (10): 840-844.PubMed Cai H, Harrison DG: Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000, 87 (10): 840-844.PubMed
25.
go back to reference Cai H: Hydrogen peroxide regulation of endothelial function: origins, mechanisms, and consequences. Cardiovasc Res. 2005, 68 (1): 26-36.PubMed Cai H: Hydrogen peroxide regulation of endothelial function: origins, mechanisms, and consequences. Cardiovasc Res. 2005, 68 (1): 26-36.PubMed
26.
go back to reference Xu J, Zou MH: Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation. 2009, 120 (13): 1266-1286.PubMedCentralPubMed Xu J, Zou MH: Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation. 2009, 120 (13): 1266-1286.PubMedCentralPubMed
27.
go back to reference Sprague AH, Khalil RA: Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol. 2009, 78 (6): 539-552.PubMedCentralPubMed Sprague AH, Khalil RA: Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol. 2009, 78 (6): 539-552.PubMedCentralPubMed
28.
29.
go back to reference Banchereau J, Pascual V, O'Garra A: From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol. 2012, 13 (10): 925-931.PubMedCentralPubMed Banchereau J, Pascual V, O'Garra A: From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines. Nat Immunol. 2012, 13 (10): 925-931.PubMedCentralPubMed
30.
go back to reference Sitia S, Tomasoni L, Atzeni F, Ambrosio G, Cordiano C, Catapano A, Tramontana S, Perticone F, Naccarato P, Camici P, Picano E, Cortigiani L, Bevilacqua M, Milazzo L, Cusi D, Barlassina C, Sarzi-Puttini P, Turiel M: From endothelial dysfunction to atherosclerosis. Autoimmun Rev. 2010, 9 (12): 830-834.PubMed Sitia S, Tomasoni L, Atzeni F, Ambrosio G, Cordiano C, Catapano A, Tramontana S, Perticone F, Naccarato P, Camici P, Picano E, Cortigiani L, Bevilacqua M, Milazzo L, Cusi D, Barlassina C, Sarzi-Puttini P, Turiel M: From endothelial dysfunction to atherosclerosis. Autoimmun Rev. 2010, 9 (12): 830-834.PubMed
31.
go back to reference Stoner L, Sabatier MJ: Use of ultrasound for non-invasive assessment of flow-mediated dilation. J Atheroscler Thromb. 2012, 19 (5): 407-421.PubMed Stoner L, Sabatier MJ: Use of ultrasound for non-invasive assessment of flow-mediated dilation. J Atheroscler Thromb. 2012, 19 (5): 407-421.PubMed
32.
go back to reference Roustit M, Cracowski JL: Assessment of endothelial and neurovascular function in human skin microcirculation. Trends Pharmacol Sci. 2013, 34 (7): 373-384.PubMed Roustit M, Cracowski JL: Assessment of endothelial and neurovascular function in human skin microcirculation. Trends Pharmacol Sci. 2013, 34 (7): 373-384.PubMed
33.
go back to reference Mulvany MJ, Halpern W: Mechanical properties of vascular smooth muscle cells in situ. Nature. 1976, 260 (5552): 617-619.PubMed Mulvany MJ, Halpern W: Mechanical properties of vascular smooth muscle cells in situ. Nature. 1976, 260 (5552): 617-619.PubMed
34.
go back to reference Spiers A, Padmanabhan N: A guide to wire myography. Methods Mol Med. 2005, 108: 91-104.PubMed Spiers A, Padmanabhan N: A guide to wire myography. Methods Mol Med. 2005, 108: 91-104.PubMed
35.
go back to reference Shahid M, Buys ES: Assessing murine resistance artery function using pressure myography.J Vis Exp 2013, (76):e50328., Shahid M, Buys ES: Assessing murine resistance artery function using pressure myography.J Vis Exp 2013, (76):e50328.,
36.
go back to reference Bridges LE, Williams CL, Pointer MA, Awumey EM: Mesenteric artery contraction and relaxation studies using automated wire myography.J Vis Exp 2011, (55):e3119., Bridges LE, Williams CL, Pointer MA, Awumey EM: Mesenteric artery contraction and relaxation studies using automated wire myography.J Vis Exp 2011, (55):e3119.,
37.
go back to reference Mulvany MJ, Aalkjaer C: Structure and function of small arteries. Physiol Rev. 1990, 70 (4): 921-961.PubMed Mulvany MJ, Aalkjaer C: Structure and function of small arteries. Physiol Rev. 1990, 70 (4): 921-961.PubMed
38.
go back to reference Lei C, Yu B, Shahid M, Beloiartsev A, Bloch KD, Zapol WM: Inhaled nitric oxide attenuates the adverse effects of transfusing stored syngeneic erythrocytes in mice with endothelial dysfunction after hemorrhagic shock. Anesthesiology. 2012, 117 (6): 1190-1202.PubMed Lei C, Yu B, Shahid M, Beloiartsev A, Bloch KD, Zapol WM: Inhaled nitric oxide attenuates the adverse effects of transfusing stored syngeneic erythrocytes in mice with endothelial dysfunction after hemorrhagic shock. Anesthesiology. 2012, 117 (6): 1190-1202.PubMed
39.
go back to reference Cheng Z, Jiang X, Kruger WD, Pratico D, Gupta S, Mallilankaraman K, Madesh M, Schafer AI, Durante W, Yang X, Wang H: Hyperhomocysteinemia impairs endothelium-derived hyperpolarizing factor-mediated vasorelaxation in transgenic cystathionine beta synthase-deficient mice. Blood. 2011, 118 (7): 1998-2006.PubMedCentralPubMed Cheng Z, Jiang X, Kruger WD, Pratico D, Gupta S, Mallilankaraman K, Madesh M, Schafer AI, Durante W, Yang X, Wang H: Hyperhomocysteinemia impairs endothelium-derived hyperpolarizing factor-mediated vasorelaxation in transgenic cystathionine beta synthase-deficient mice. Blood. 2011, 118 (7): 1998-2006.PubMedCentralPubMed
40.
go back to reference Gutierrez E, Flammer AJ, Lerman LO, Elizaga J, Lerman A, Fernandez-Aviles F: Endothelial dysfunction over the course of coronary artery disease. Eur Heart J. 2013, 34 (41): 3175-3181.PubMedCentralPubMed Gutierrez E, Flammer AJ, Lerman LO, Elizaga J, Lerman A, Fernandez-Aviles F: Endothelial dysfunction over the course of coronary artery disease. Eur Heart J. 2013, 34 (41): 3175-3181.PubMedCentralPubMed
41.
42.
go back to reference Pacher P, Beckman JS, Liaudet L: Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007, 87 (1): 315-424.PubMedCentralPubMed Pacher P, Beckman JS, Liaudet L: Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007, 87 (1): 315-424.PubMedCentralPubMed
43.
go back to reference Rafikov R, Fonseca FV, Kumar S, Pardo D, Darragh C, Elms S, Fulton D, Black SM: eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity. J Endocrinol. 2011, 210 (3): 271-284.PubMedCentralPubMed Rafikov R, Fonseca FV, Kumar S, Pardo D, Darragh C, Elms S, Fulton D, Black SM: eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity. J Endocrinol. 2011, 210 (3): 271-284.PubMedCentralPubMed
44.
go back to reference Kashiwagi S, Atochin DN, Li Q, Schleicher M, Pong T, Sessa WC, Huang PL: eNOS phosphorylation on serine 1176 affects insulin sensitivity and adiposity. Biochem Biophys Res Commun. 2013, 431 (2): 284-290.PubMedCentralPubMed Kashiwagi S, Atochin DN, Li Q, Schleicher M, Pong T, Sessa WC, Huang PL: eNOS phosphorylation on serine 1176 affects insulin sensitivity and adiposity. Biochem Biophys Res Commun. 2013, 431 (2): 284-290.PubMedCentralPubMed
45.
go back to reference Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM: Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999, 399 (6736): 601-605.PubMed Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM: Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999, 399 (6736): 601-605.PubMed
46.
go back to reference Fleming I, Fisslthaler B, Dimmeler S, Kemp BE, Busse R: Phosphorylation of Thr(495) regulates Ca(2+)/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res. 2001, 88 (11): E68-E75.PubMed Fleming I, Fisslthaler B, Dimmeler S, Kemp BE, Busse R: Phosphorylation of Thr(495) regulates Ca(2+)/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res. 2001, 88 (11): E68-E75.PubMed
47.
go back to reference Olson SC, Dowds TA, Pino PA, Barry MT, Burke-Wolin T: ANG II stimulates endothelial nitric oxide synthase expression in bovine pulmonary artery endothelium. Am J Physiol. 1997, 273 (2 Pt 1): L315-L321.PubMed Olson SC, Dowds TA, Pino PA, Barry MT, Burke-Wolin T: ANG II stimulates endothelial nitric oxide synthase expression in bovine pulmonary artery endothelium. Am J Physiol. 1997, 273 (2 Pt 1): L315-L321.PubMed
48.
go back to reference Marasciulo FL, Montagnani M, Potenza MA: Endothelin-1: the yin and yang on vascular function. Curr Med Chem. 2006, 13 (14): 1655-1665.PubMed Marasciulo FL, Montagnani M, Potenza MA: Endothelin-1: the yin and yang on vascular function. Curr Med Chem. 2006, 13 (14): 1655-1665.PubMed
49.
go back to reference Salvemini D, Misko TP, Masferrer JL, Seibert K, Currie MG, Needleman P: Nitric oxide activates cyclooxygenase enzymes. Proc Natl Acad Sci U S A. 1993, 90 (15): 7240-7244.PubMedCentralPubMed Salvemini D, Misko TP, Masferrer JL, Seibert K, Currie MG, Needleman P: Nitric oxide activates cyclooxygenase enzymes. Proc Natl Acad Sci U S A. 1993, 90 (15): 7240-7244.PubMedCentralPubMed
50.
go back to reference Andrew PJ, Mayer B: Enzymatic function of nitric oxide synthases. Cardiovasc Res. 1999, 43 (3): 521-531.PubMed Andrew PJ, Mayer B: Enzymatic function of nitric oxide synthases. Cardiovasc Res. 1999, 43 (3): 521-531.PubMed
51.
go back to reference Anselm E, Chataigneau M, Ndiaye M, Chataigneau T, Schini-Kerth VB: Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS. Cardiovasc Res. 2007, 73 (2): 404-413.PubMed Anselm E, Chataigneau M, Ndiaye M, Chataigneau T, Schini-Kerth VB: Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS. Cardiovasc Res. 2007, 73 (2): 404-413.PubMed
52.
go back to reference Feletou M, Vanhoutte PM: EDHF: an update. Clin Sci (Lond). 2009, 117 (4): 139-155. Feletou M, Vanhoutte PM: EDHF: an update. Clin Sci (Lond). 2009, 117 (4): 139-155.
53.
go back to reference Ozkor MA, Quyyumi AA: Endothelium-derived hyperpolarizing factor and vascular function. Cardiol Res Pract. 2011, 2011: 156146-PubMedCentralPubMed Ozkor MA, Quyyumi AA: Endothelium-derived hyperpolarizing factor and vascular function. Cardiol Res Pract. 2011, 2011: 156146-PubMedCentralPubMed
54.
go back to reference Sandow SL, Tare M, Coleman HA, Hill CE, Parkington HC: Involvement of myoendothelial gap junctions in the actions of endothelium-derived hyperpolarizing factor. Circ Res. 2002, 90 (10): 1108-1113.PubMed Sandow SL, Tare M, Coleman HA, Hill CE, Parkington HC: Involvement of myoendothelial gap junctions in the actions of endothelium-derived hyperpolarizing factor. Circ Res. 2002, 90 (10): 1108-1113.PubMed
55.
go back to reference Doughty JM, Plane F, Langton PD: Charybdotoxin and apamin block EDHF in rat mesenteric artery if selectively applied to the endothelium. Am J Physiol. 1999, 276 (3 Pt 2): H1107-H1112.PubMed Doughty JM, Plane F, Langton PD: Charybdotoxin and apamin block EDHF in rat mesenteric artery if selectively applied to the endothelium. Am J Physiol. 1999, 276 (3 Pt 2): H1107-H1112.PubMed
56.
go back to reference Corriu C, Feletou M, Canet E, Vanhoutte PM: Endothelium-derived factors and hyperpolarization of the carotid artery of the guinea-pig. Br J Pharmacol. 1996, 119 (5): 959-964.PubMedCentralPubMed Corriu C, Feletou M, Canet E, Vanhoutte PM: Endothelium-derived factors and hyperpolarization of the carotid artery of the guinea-pig. Br J Pharmacol. 1996, 119 (5): 959-964.PubMedCentralPubMed
57.
go back to reference Murphy ME, Brayden JE: Apamin-sensitive K + channels mediate an endothelium-dependent hyperpolarization in rabbit mesenteric arteries. J Physiol. 1995, 489 (Pt 3): 723-734.PubMedCentralPubMed Murphy ME, Brayden JE: Apamin-sensitive K + channels mediate an endothelium-dependent hyperpolarization in rabbit mesenteric arteries. J Physiol. 1995, 489 (Pt 3): 723-734.PubMedCentralPubMed
58.
go back to reference Hannah RM, Dunn KM, Bonev AD, Nelson MT: Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow. J Cereb Blood Flow Metab. 2011, 31 (5): 1175-1186.PubMedCentralPubMed Hannah RM, Dunn KM, Bonev AD, Nelson MT: Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow. J Cereb Blood Flow Metab. 2011, 31 (5): 1175-1186.PubMedCentralPubMed
59.
go back to reference Chataigneau T, Feletou M, Duhault J, Vanhoutte PM: Epoxyeicosatrienoic acids, potassium channel blockers and endothelium-dependent hyperpolarization in the guinea-pig carotid artery. Br J Pharmacol. 1998, 123 (3): 574-580.PubMedCentralPubMed Chataigneau T, Feletou M, Duhault J, Vanhoutte PM: Epoxyeicosatrienoic acids, potassium channel blockers and endothelium-dependent hyperpolarization in the guinea-pig carotid artery. Br J Pharmacol. 1998, 123 (3): 574-580.PubMedCentralPubMed
60.
go back to reference Nelson MT, Quayle JM: Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol. 1995, 268 (4 Pt 1): C799-C822.PubMed Nelson MT, Quayle JM: Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol. 1995, 268 (4 Pt 1): C799-C822.PubMed
61.
go back to reference Neylon CB, Lang RJ, Fu Y, Bobik A, Reinhart PH: Molecular cloning and characterization of the intermediate-conductance Ca(2+)-activated K(+) channel in vascular smooth muscle: relationship between K(Ca) channel diversity and smooth muscle cell function. Circ Res. 1999, 85 (9): e33-e43.PubMed Neylon CB, Lang RJ, Fu Y, Bobik A, Reinhart PH: Molecular cloning and characterization of the intermediate-conductance Ca(2+)-activated K(+) channel in vascular smooth muscle: relationship between K(Ca) channel diversity and smooth muscle cell function. Circ Res. 1999, 85 (9): e33-e43.PubMed
62.
go back to reference Larsen BT, Gutterman DD, Sato A, Toyama K, Campbell WB, Zeldin DC, Manthati VL, Falck JR, Miura H: Hydrogen peroxide inhibits cytochrome p450 epoxygenases: interaction between two endothelium-derived hyperpolarizing factors. Circ Res. 2008, 102 (1): 59-67.PubMedCentralPubMed Larsen BT, Gutterman DD, Sato A, Toyama K, Campbell WB, Zeldin DC, Manthati VL, Falck JR, Miura H: Hydrogen peroxide inhibits cytochrome p450 epoxygenases: interaction between two endothelium-derived hyperpolarizing factors. Circ Res. 2008, 102 (1): 59-67.PubMedCentralPubMed
63.
go back to reference Yada T, Shimokawa H, Hiramatsu O, Kajita T, Shigeto F, Goto M, Ogasawara Y, Kajiya F: Hydrogen peroxide, an endogenous endothelium-derived hyperpolarizing factor, plays an important role in coronary autoregulation in vivo. Circulation. 2003, 107 (7): 1040-1045.PubMed Yada T, Shimokawa H, Hiramatsu O, Kajita T, Shigeto F, Goto M, Ogasawara Y, Kajiya F: Hydrogen peroxide, an endogenous endothelium-derived hyperpolarizing factor, plays an important role in coronary autoregulation in vivo. Circulation. 2003, 107 (7): 1040-1045.PubMed
64.
go back to reference Matoba T, Shimokawa H, Nakashima M, Hirakawa Y, Mukai Y, Hirano K, Kanaide H, Takeshita A: Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J Clin Invest. 2000, 106 (12): 1521-1530.PubMedCentralPubMed Matoba T, Shimokawa H, Nakashima M, Hirakawa Y, Mukai Y, Hirano K, Kanaide H, Takeshita A: Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J Clin Invest. 2000, 106 (12): 1521-1530.PubMedCentralPubMed
65.
go back to reference Morikawa K, Shimokawa H, Matoba T, Kubota H, Akaike T, Talukder MA, Hatanaka M, Fujiki T, Maeda H, Takahashi S, Takeshita A: Pivotal role of Cu, Zn-superoxide dismutase in endothelium-dependent hyperpolarization. J Clin Invest. 2003, 112 (12): 1871-1879.PubMedCentralPubMed Morikawa K, Shimokawa H, Matoba T, Kubota H, Akaike T, Talukder MA, Hatanaka M, Fujiki T, Maeda H, Takahashi S, Takeshita A: Pivotal role of Cu, Zn-superoxide dismutase in endothelium-dependent hyperpolarization. J Clin Invest. 2003, 112 (12): 1871-1879.PubMedCentralPubMed
66.
go back to reference Wynne BM, Labazi H, Tostes RC, Webb RC: Aorta from angiotensin II hypertensive mice exhibit preserved nitroxyl anion mediated relaxation responses. Pharmacol Res. 2012, 65 (1): 41-47.PubMedCentralPubMed Wynne BM, Labazi H, Tostes RC, Webb RC: Aorta from angiotensin II hypertensive mice exhibit preserved nitroxyl anion mediated relaxation responses. Pharmacol Res. 2012, 65 (1): 41-47.PubMedCentralPubMed
67.
go back to reference Andrews KL, Irvine JC, Tare M, Apostolopoulos J, Favaloro JL, Triggle CR, Kemp-Harper BK: A role for nitroxyl (HNO) as an endothelium-derived relaxing and hyperpolarizing factor in resistance arteries. Br J Pharmacol. 2009, 157 (4): 540-550.PubMedCentralPubMed Andrews KL, Irvine JC, Tare M, Apostolopoulos J, Favaloro JL, Triggle CR, Kemp-Harper BK: A role for nitroxyl (HNO) as an endothelium-derived relaxing and hyperpolarizing factor in resistance arteries. Br J Pharmacol. 2009, 157 (4): 540-550.PubMedCentralPubMed
68.
go back to reference Mustafa AK, Sikka G, Gazi SK, Steppan J, Jung SM, Bhunia AK, Barodka VM, Gazi FK, Barrow RK, Wang R, Amzel LM, Berkowitz DE, Snyder SH: Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ Res. 2011, 109 (11): 1259-1268.PubMedCentralPubMed Mustafa AK, Sikka G, Gazi SK, Steppan J, Jung SM, Bhunia AK, Barodka VM, Gazi FK, Barrow RK, Wang R, Amzel LM, Berkowitz DE, Snyder SH: Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ Res. 2011, 109 (11): 1259-1268.PubMedCentralPubMed
69.
go back to reference Shimokawa H, Yasutake H, Fujii K, Owada MK, Nakaike R, Fukumoto Y, Takayanagi T, Nagao T, Egashira K, Fujishima M, Takeshita A: The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol. 1996, 28 (5): 703-711.PubMed Shimokawa H, Yasutake H, Fujii K, Owada MK, Nakaike R, Fukumoto Y, Takayanagi T, Nagao T, Egashira K, Fujishima M, Takeshita A: The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol. 1996, 28 (5): 703-711.PubMed
70.
go back to reference Bellien J, Joannides R, Iacob M, Arnaud P, Thuillez C: Evidence for a basal release of a cytochrome-related endothelium-derived hyperpolarizing factor in the radial artery in humans. Am J Physiol Heart Circ Physiol. 2006, 290 (4): H1347-H1352.PubMed Bellien J, Joannides R, Iacob M, Arnaud P, Thuillez C: Evidence for a basal release of a cytochrome-related endothelium-derived hyperpolarizing factor in the radial artery in humans. Am J Physiol Heart Circ Physiol. 2006, 290 (4): H1347-H1352.PubMed
71.
go back to reference Ozkor MA, Murrow JR, Rahman AM, Kavtaradze N, Lin J, Manatunga A, Quyyumi AA: Endothelium-derived hyperpolarizing factor determines resting and stimulated forearm vasodilator tone in health and in disease. Circulation. 2011, 123 (20): 2244-2253.PubMedCentralPubMed Ozkor MA, Murrow JR, Rahman AM, Kavtaradze N, Lin J, Manatunga A, Quyyumi AA: Endothelium-derived hyperpolarizing factor determines resting and stimulated forearm vasodilator tone in health and in disease. Circulation. 2011, 123 (20): 2244-2253.PubMedCentralPubMed
72.
go back to reference Caughey GE, Cleland LG, Penglis PS, Gamble JR, James MJ: Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid production by human endothelial cells: selective up-regulation of prostacyclin synthesis by COX-2. J Immunol. 2001, 167 (5): 2831-2838.PubMed Caughey GE, Cleland LG, Penglis PS, Gamble JR, James MJ: Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid production by human endothelial cells: selective up-regulation of prostacyclin synthesis by COX-2. J Immunol. 2001, 167 (5): 2831-2838.PubMed
73.
go back to reference Kirkby NS, Lundberg MH, Harrington LS, Leadbeater PD, Milne GL, Potter CM, Al-Yamani M, Adeyemi O, Warner TD, Mitchell JA: Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system. Proc Natl Acad Sci U S A. 2012, 109 (43): 17597-17602.PubMedCentralPubMed Kirkby NS, Lundberg MH, Harrington LS, Leadbeater PD, Milne GL, Potter CM, Al-Yamani M, Adeyemi O, Warner TD, Mitchell JA: Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system. Proc Natl Acad Sci U S A. 2012, 109 (43): 17597-17602.PubMedCentralPubMed
74.
go back to reference Ricciotti E, Yu Y, Grosser T, Fitzgerald GA: COX-2, the dominant source of prostacyclin. Proc Natl Acad Sci U S A. 2013, 110 (3): E183-PubMedCentralPubMed Ricciotti E, Yu Y, Grosser T, Fitzgerald GA: COX-2, the dominant source of prostacyclin. Proc Natl Acad Sci U S A. 2013, 110 (3): E183-PubMedCentralPubMed
75.
go back to reference Tare M, Parkington HC, Coleman HA: EDHF, NO and a prostanoid: hyperpolarization-dependent and -independent relaxation in guinea-pig arteries. Br J Pharmacol. 2000, 130 (3): 605-618.PubMedCentralPubMed Tare M, Parkington HC, Coleman HA: EDHF, NO and a prostanoid: hyperpolarization-dependent and -independent relaxation in guinea-pig arteries. Br J Pharmacol. 2000, 130 (3): 605-618.PubMedCentralPubMed
76.
go back to reference Dautzenberg M, Just A: Temporal characteristics of nitric oxide-, prostaglandin-, and EDHF-mediated components of endothelium-dependent vasodilation in the kidney. Am J Physiol Regul Integr Comp Physiol. 2013, 305 (9): R987-R998.PubMed Dautzenberg M, Just A: Temporal characteristics of nitric oxide-, prostaglandin-, and EDHF-mediated components of endothelium-dependent vasodilation in the kidney. Am J Physiol Regul Integr Comp Physiol. 2013, 305 (9): R987-R998.PubMed
77.
go back to reference Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF: Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol. 2013, 6: 19-PubMedCentralPubMed Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF: Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol. 2013, 6: 19-PubMedCentralPubMed
78.
79.
go back to reference Zhang JG, Nicholls-Grzemski FA, Tirmenstein MA, Fariss MW: Vitamin E succinate protects hepatocytes against the toxic effect of reactive oxygen species generated at mitochondrial complexes I and III by alkylating agents. Chem Biol Interact. 2001, 138 (3): 267-284.PubMed Zhang JG, Nicholls-Grzemski FA, Tirmenstein MA, Fariss MW: Vitamin E succinate protects hepatocytes against the toxic effect of reactive oxygen species generated at mitochondrial complexes I and III by alkylating agents. Chem Biol Interact. 2001, 138 (3): 267-284.PubMed
80.
go back to reference Yang B, Rizzo V: TNF-alpha potentiates protein-tyrosine nitration through activation of NADPH oxidase and eNOS localized in membrane rafts and caveolae of bovine aortic endothelial cells. Am J Physiol Heart Circ Physiol. 2007, 292 (2): H954-H962.PubMed Yang B, Rizzo V: TNF-alpha potentiates protein-tyrosine nitration through activation of NADPH oxidase and eNOS localized in membrane rafts and caveolae of bovine aortic endothelial cells. Am J Physiol Heart Circ Physiol. 2007, 292 (2): H954-H962.PubMed
81.
go back to reference Cai H: NAD(P)H oxidase-dependent self-propagation of hydrogen peroxide and vascular disease. Circ Res. 2005, 96 (8): 818-822.PubMed Cai H: NAD(P)H oxidase-dependent self-propagation of hydrogen peroxide and vascular disease. Circ Res. 2005, 96 (8): 818-822.PubMed
82.
go back to reference Houstis N, Rosen ED, Lander ES: Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 2006, 440 (7086): 944-948.PubMed Houstis N, Rosen ED, Lander ES: Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 2006, 440 (7086): 944-948.PubMed
83.
go back to reference Mugge A, Elwell JH, Peterson TE, Hofmeyer TG, Heistad DD, Harrison DG: Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. Circ Res. 1991, 69 (5): 1293-1300.PubMed Mugge A, Elwell JH, Peterson TE, Hofmeyer TG, Heistad DD, Harrison DG: Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. Circ Res. 1991, 69 (5): 1293-1300.PubMed
84.
go back to reference Miller FJ, Gutterman DD, Rios CD, Heistad DD, Davidson BL: Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res. 1998, 82 (12): 1298-1305.PubMed Miller FJ, Gutterman DD, Rios CD, Heistad DD, Davidson BL: Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res. 1998, 82 (12): 1298-1305.PubMed
85.
go back to reference Langenstroer P, Pieper GM: Regulation of spontaneous EDRF release in diabetic rat aorta by oxygen free radicals. Am J Physiol. 1992, 263 (1 Pt 2): H257-H265.PubMed Langenstroer P, Pieper GM: Regulation of spontaneous EDRF release in diabetic rat aorta by oxygen free radicals. Am J Physiol. 1992, 263 (1 Pt 2): H257-H265.PubMed
86.
go back to reference Oak JH, Cai H: Attenuation of angiotensin II signaling recouples eNOS and inhibits nonendothelial NOX activity in diabetic mice. Diabetes. 2007, 56 (1): 118-126.PubMed Oak JH, Cai H: Attenuation of angiotensin II signaling recouples eNOS and inhibits nonendothelial NOX activity in diabetic mice. Diabetes. 2007, 56 (1): 118-126.PubMed
87.
go back to reference Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim KY, Sack MN, Kastner DL, Siegel RM: Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med. 2011, 208 (3): 519-533.PubMedCentralPubMed Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim KY, Sack MN, Kastner DL, Siegel RM: Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med. 2011, 208 (3): 519-533.PubMedCentralPubMed
88.
go back to reference David F, Farley J, Huang H, Lavoie JP, Laverty S: Cytokine and chemokine gene expression of IL-1beta stimulated equine articular chondrocytes. Vet Surg. 2007, 36 (3): 221-227.PubMed David F, Farley J, Huang H, Lavoie JP, Laverty S: Cytokine and chemokine gene expression of IL-1beta stimulated equine articular chondrocytes. Vet Surg. 2007, 36 (3): 221-227.PubMed
89.
go back to reference Vlahopoulos S, Boldogh I, Casola A, Brasier AR: Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation. Blood. 1999, 94 (6): 1878-1889.PubMed Vlahopoulos S, Boldogh I, Casola A, Brasier AR: Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation. Blood. 1999, 94 (6): 1878-1889.PubMed
90.
91.
go back to reference Bagnost T, Berthelot A, Bouhaddi M, Laurant P, Andre C, Guillaume Y, Demougeot C: Treatment with the arginase inhibitor N(omega)-hydroxy-nor-L-arginine improves vascular function and lowers blood pressure in adult spontaneously hypertensive rat. J Hypertens. 2008, 26 (6): 1110-1118.PubMed Bagnost T, Berthelot A, Bouhaddi M, Laurant P, Andre C, Guillaume Y, Demougeot C: Treatment with the arginase inhibitor N(omega)-hydroxy-nor-L-arginine improves vascular function and lowers blood pressure in adult spontaneously hypertensive rat. J Hypertens. 2008, 26 (6): 1110-1118.PubMed
92.
go back to reference Demougeot C, Prigent-Tessier A, Marie C, Berthelot A: Arginase inhibition reduces endothelial dysfunction and blood pressure rising in spontaneously hypertensive rats. J Hypertens. 2005, 23 (5): 971-978.PubMed Demougeot C, Prigent-Tessier A, Marie C, Berthelot A: Arginase inhibition reduces endothelial dysfunction and blood pressure rising in spontaneously hypertensive rats. J Hypertens. 2005, 23 (5): 971-978.PubMed
93.
go back to reference Toque HA, Romero MJ, Tostes RC, Shatanawi A, Chandra S, Carneiro ZN, Inscho EW, Webb RC, Caldwell RB, Caldwell RW: p38 Mitogen-activated protein kinase (MAPK) increases arginase activity and contributes to endothelial dysfunction in corpora cavernosa from angiotensin-II-treated mice. J Sex Med. 2010, 7 (12): 3857-3867.PubMedCentralPubMed Toque HA, Romero MJ, Tostes RC, Shatanawi A, Chandra S, Carneiro ZN, Inscho EW, Webb RC, Caldwell RB, Caldwell RW: p38 Mitogen-activated protein kinase (MAPK) increases arginase activity and contributes to endothelial dysfunction in corpora cavernosa from angiotensin-II-treated mice. J Sex Med. 2010, 7 (12): 3857-3867.PubMedCentralPubMed
94.
go back to reference Satoh M, Fujimoto S, Arakawa S, Yada T, Namikoshi T, Haruna Y, Horike H, Sasaki T, Kashihara N: Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with experimental diabetic nephropathy. Nephrol Dial Transplant. 2008, 23 (12): 3806-3813.PubMedCentralPubMed Satoh M, Fujimoto S, Arakawa S, Yada T, Namikoshi T, Haruna Y, Horike H, Sasaki T, Kashihara N: Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with experimental diabetic nephropathy. Nephrol Dial Transplant. 2008, 23 (12): 3806-3813.PubMedCentralPubMed
95.
go back to reference Virdis A, Colucci R, Neves MF, Rugani I, Aydinoglu F, Fornai M, Ippolito C, Antonioli L, Duranti E, Solini A, Bernardini N, Blandizzi C, Taddei S: Resistance artery mechanics and composition in angiotensin II-infused mice: effects of cyclooxygenase-1 inhibition. Eur Heart J. 2012, 33 (17): 2225-2234.PubMed Virdis A, Colucci R, Neves MF, Rugani I, Aydinoglu F, Fornai M, Ippolito C, Antonioli L, Duranti E, Solini A, Bernardini N, Blandizzi C, Taddei S: Resistance artery mechanics and composition in angiotensin II-infused mice: effects of cyclooxygenase-1 inhibition. Eur Heart J. 2012, 33 (17): 2225-2234.PubMed
96.
go back to reference Cheng ZJ, Vapaatalo H, Mervaala E: Angiotensin II and vascular inflammation. Med Sci Monit. 2005, 11 (6): RA194-RA205.PubMed Cheng ZJ, Vapaatalo H, Mervaala E: Angiotensin II and vascular inflammation. Med Sci Monit. 2005, 11 (6): RA194-RA205.PubMed
97.
go back to reference Kourembanas S, McQuillan LP, Leung GK, Faller DV: Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia. J Clin Invest. 1993, 92 (1): 99-104.PubMedCentralPubMed Kourembanas S, McQuillan LP, Leung GK, Faller DV: Nitric oxide regulates the expression of vasoconstrictors and growth factors by vascular endothelium under both normoxia and hypoxia. J Clin Invest. 1993, 92 (1): 99-104.PubMedCentralPubMed
98.
go back to reference Wiley KE, Davenport AP: Nitric oxide-mediated modulation of the endothelin-1 signalling pathway in the human cardiovascular system. Br J Pharmacol. 2001, 132 (1): 213-220.PubMedCentralPubMed Wiley KE, Davenport AP: Nitric oxide-mediated modulation of the endothelin-1 signalling pathway in the human cardiovascular system. Br J Pharmacol. 2001, 132 (1): 213-220.PubMedCentralPubMed
99.
go back to reference Minshall RD, Sessa WC, Stan RV, Anderson RG, Malik AB: Caveolin regulation of endothelial function. Am J Physiol Lung Cell Mol Physiol. 2003, 285 (6): L1179-L1183.PubMed Minshall RD, Sessa WC, Stan RV, Anderson RG, Malik AB: Caveolin regulation of endothelial function. Am J Physiol Lung Cell Mol Physiol. 2003, 285 (6): L1179-L1183.PubMed
100.
go back to reference Amiri F, Virdis A, Neves MF, Iglarz M, Seidah NG, Touyz RM, Reudelhuber TL, Schiffrin EL: Endothelium-restricted overexpression of human endothelin-1 causes vascular remodeling and endothelial dysfunction. Circulation. 2004, 110 (15): 2233-2240.PubMed Amiri F, Virdis A, Neves MF, Iglarz M, Seidah NG, Touyz RM, Reudelhuber TL, Schiffrin EL: Endothelium-restricted overexpression of human endothelin-1 causes vascular remodeling and endothelial dysfunction. Circulation. 2004, 110 (15): 2233-2240.PubMed
101.
go back to reference Amiri F, Ko EA, Javeshghani D, Reudelhuber TL, Schiffrin EL: Deleterious combined effects of salt-loading and endothelial cell restricted endothelin-1 overexpression on blood pressure and vascular function in mice. J Hypertens. 2010, 28 (6): 1243-1251.PubMed Amiri F, Ko EA, Javeshghani D, Reudelhuber TL, Schiffrin EL: Deleterious combined effects of salt-loading and endothelial cell restricted endothelin-1 overexpression on blood pressure and vascular function in mice. J Hypertens. 2010, 28 (6): 1243-1251.PubMed
102.
go back to reference Javeshghani D, Barhoumi T, Idris-Khodja N, Paradis P, Schiffrin EL: Reduced macrophage-dependent inflammation improves endothelin-1-induced vascular injury. Hypertension. 2013, 62 (1): 112-117.PubMed Javeshghani D, Barhoumi T, Idris-Khodja N, Paradis P, Schiffrin EL: Reduced macrophage-dependent inflammation improves endothelin-1-induced vascular injury. Hypertension. 2013, 62 (1): 112-117.PubMed
103.
go back to reference De Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL: Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II-infused macrophage colony-stimulating factor-deficient mice: evidence for a role in inflammation in angiotensin-induced vascular injury. Arterioscler Thromb Vasc Biol. 2005, 25 (10): 2106-2113.PubMed De Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL: Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II-infused macrophage colony-stimulating factor-deficient mice: evidence for a role in inflammation in angiotensin-induced vascular injury. Arterioscler Thromb Vasc Biol. 2005, 25 (10): 2106-2113.PubMed
104.
go back to reference Barhoumi T, Kasal DA, Li MW, Shbat L, Laurant P, Neves MF, Paradis P, Schiffrin EL: T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension. 2011, 57 (3): 469-476.PubMed Barhoumi T, Kasal DA, Li MW, Shbat L, Laurant P, Neves MF, Paradis P, Schiffrin EL: T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension. 2011, 57 (3): 469-476.PubMed
105.
go back to reference Bhagat K, Vallance P: Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo. Circulation. 1997, 96 (9): 3042-3047.PubMed Bhagat K, Vallance P: Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo. Circulation. 1997, 96 (9): 3042-3047.PubMed
106.
go back to reference Stenvinkel P: Endothelial dysfunction and inflammation-is there a link?. Nephrol Dial Transplant. 2001, 16 (10): 1968-1971.PubMed Stenvinkel P: Endothelial dysfunction and inflammation-is there a link?. Nephrol Dial Transplant. 2001, 16 (10): 1968-1971.PubMed
107.
go back to reference Herder C, Carstensen M, Ouwens DM: Anti-inflammatory cytokines and risk of type 2 diabetes. Diabetes Obes Metab. 2013, 15 (Suppl 3): 39-50.PubMed Herder C, Carstensen M, Ouwens DM: Anti-inflammatory cytokines and risk of type 2 diabetes. Diabetes Obes Metab. 2013, 15 (Suppl 3): 39-50.PubMed
108.
go back to reference Gleissner CA, Zastrow A, Klingenberg R, Kluger MS, Konstandin M, Celik S, Haemmerling S, Shankar V, Giese T, Katus HA, Dengler TJ: IL-10 inhibits endothelium-dependent T cell costimulation by up-regulation of ILT3/4 in human vascular endothelial cells. Eur J Immunol. 2007, 37 (1): 177-192.PubMed Gleissner CA, Zastrow A, Klingenberg R, Kluger MS, Konstandin M, Celik S, Haemmerling S, Shankar V, Giese T, Katus HA, Dengler TJ: IL-10 inhibits endothelium-dependent T cell costimulation by up-regulation of ILT3/4 in human vascular endothelial cells. Eur J Immunol. 2007, 37 (1): 177-192.PubMed
109.
go back to reference Moore KW, de Waal MR, Coffman RL, O'Garra A: Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001, 19: 683-765.PubMed Moore KW, de Waal MR, Coffman RL, O'Garra A: Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001, 19: 683-765.PubMed
110.
go back to reference Caligiuri G, Rudling M, Ollivier V, Jacob MP, Michel JB, Hansson GK, Nicoletti A: Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med. 2003, 9 (1–2): 10-17.PubMedCentralPubMed Caligiuri G, Rudling M, Ollivier V, Jacob MP, Michel JB, Hansson GK, Nicoletti A: Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med. 2003, 9 (1–2): 10-17.PubMedCentralPubMed
111.
go back to reference Gunnett CA, Heistad DD, Faraci FM: Interleukin-10 protects nitric oxide-dependent relaxation during diabetes: role of superoxide. Diabetes. 2002, 51 (6): 1931-1937.PubMed Gunnett CA, Heistad DD, Faraci FM: Interleukin-10 protects nitric oxide-dependent relaxation during diabetes: role of superoxide. Diabetes. 2002, 51 (6): 1931-1937.PubMed
112.
go back to reference Didion SP, Kinzenbaw DA, Schrader LI, Chu Y, Faraci FM: Endogenous interleukin-10 inhibits angiotensin II-induced vascular dysfunction. Hypertension. 2009, 54 (3): 619-624.PubMedCentralPubMed Didion SP, Kinzenbaw DA, Schrader LI, Chu Y, Faraci FM: Endogenous interleukin-10 inhibits angiotensin II-induced vascular dysfunction. Hypertension. 2009, 54 (3): 619-624.PubMedCentralPubMed
113.
go back to reference Oberholzer A, Oberholzer C, Moldawer LL: Interleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. Crit Care Med. 2002, 30 (1 Supp): S58-S63. Oberholzer A, Oberholzer C, Moldawer LL: Interleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. Crit Care Med. 2002, 30 (1 Supp): S58-S63.
114.
go back to reference Gunnett CA, Heistad DD, Berg DJ, Faraci FM: IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation. Am J Physiol Heart Circ Physiol. 2000, 279 (4): H1555-H1562.PubMed Gunnett CA, Heistad DD, Berg DJ, Faraci FM: IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation. Am J Physiol Heart Circ Physiol. 2000, 279 (4): H1555-H1562.PubMed
115.
go back to reference Haddad JJ, Fahlman CS: Redox- and oxidant-mediated regulation of interleukin-10: an anti-inflammatory, antioxidant cytokine?. Biochem Biophys Res Commun. 2002, 297 (2): 163-176.PubMed Haddad JJ, Fahlman CS: Redox- and oxidant-mediated regulation of interleukin-10: an anti-inflammatory, antioxidant cytokine?. Biochem Biophys Res Commun. 2002, 297 (2): 163-176.PubMed
116.
go back to reference Fichtlscherer S, Breuer S, Heeschen C, Dimmeler S, Zeiher AM: Interleukin-10 serum levels and systemic endothelial vasoreactivity in patients with coronary artery disease. J Am Coll Cardiol. 2004, 44 (1): 44-49.PubMed Fichtlscherer S, Breuer S, Heeschen C, Dimmeler S, Zeiher AM: Interleukin-10 serum levels and systemic endothelial vasoreactivity in patients with coronary artery disease. J Am Coll Cardiol. 2004, 44 (1): 44-49.PubMed
117.
go back to reference Dang PM, Elbim C, Marie JC, Chiandotto M, Gougerot-Pocidalo MA, El-Benna J: Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF-induced p47PHOX phosphorylation through a decrease in ERK1/2 activity. FASEB J. 2006, 20 (9): 1504-1506.PubMed Dang PM, Elbim C, Marie JC, Chiandotto M, Gougerot-Pocidalo MA, El-Benna J: Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF-induced p47PHOX phosphorylation through a decrease in ERK1/2 activity. FASEB J. 2006, 20 (9): 1504-1506.PubMed
118.
go back to reference Zemse SM, Hilgers RH, Webb RC: Interleukin-10 counteracts impaired endothelium-dependent relaxation induced by ANG II in murine aortic rings. Am J Physiol Heart Circ Physiol. 2007, 292 (6): H3103-H3108.PubMed Zemse SM, Hilgers RH, Webb RC: Interleukin-10 counteracts impaired endothelium-dependent relaxation induced by ANG II in murine aortic rings. Am J Physiol Heart Circ Physiol. 2007, 292 (6): H3103-H3108.PubMed
119.
go back to reference Kassan M, Galan M, Partyka M, Trebak M, Matrougui K: Interleukin-10 released by CD4(+)CD25(+) natural regulatory T cells improves microvascular endothelial function through inhibition of NADPH oxidase activity in hypertensive mice. Arterioscler Thromb Vasc Biol. 2011, 31 (11): 2534-2542.PubMedCentralPubMed Kassan M, Galan M, Partyka M, Trebak M, Matrougui K: Interleukin-10 released by CD4(+)CD25(+) natural regulatory T cells improves microvascular endothelial function through inhibition of NADPH oxidase activity in hypertensive mice. Arterioscler Thromb Vasc Biol. 2011, 31 (11): 2534-2542.PubMedCentralPubMed
120.
go back to reference Kinzenbaw DA, Chu Y, Pena Silva RA, Didion SP, Faraci FM: Interleukin-10 protects against aging-induced endothelial dysfunction. Physiol Rep. 2013, 1 (6): e00149-PubMedCentralPubMed Kinzenbaw DA, Chu Y, Pena Silva RA, Didion SP, Faraci FM: Interleukin-10 protects against aging-induced endothelial dysfunction. Physiol Rep. 2013, 1 (6): e00149-PubMedCentralPubMed
121.
go back to reference Sikka G, Miller KL, Steppan J, Pandey D, Jung SM, Fraser CD, Ellis C, Ross D, Vandegaer K, Bedja D, Gabrielson K, Walston JD, Berkowitz DE, Barouch LA: Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. Exp Gerontol. 2013, 48 (2): 128-135.PubMedCentralPubMed Sikka G, Miller KL, Steppan J, Pandey D, Jung SM, Fraser CD, Ellis C, Ross D, Vandegaer K, Bedja D, Gabrielson K, Walston JD, Berkowitz DE, Barouch LA: Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. Exp Gerontol. 2013, 48 (2): 128-135.PubMedCentralPubMed
122.
go back to reference Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O'Garra A: IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991, 147 (11): 3815-3822.PubMed Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O'Garra A: IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991, 147 (11): 3815-3822.PubMed
123.
go back to reference Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O'Garra A: IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991, 146 (10): 3444-3451.PubMed Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O'Garra A: IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991, 146 (10): 3444-3451.PubMed
124.
go back to reference de Waal MR, Abrams J, Bennett B, Figdor CG, de Vries JE: Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991, 174 (5): 1209-1220. de Waal MR, Abrams J, Bennett B, Figdor CG, de Vries JE: Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991, 174 (5): 1209-1220.
125.
go back to reference Asadullah K, Sterry W, Volk HD: Interleukin-10 therapy–review of a new approach. Pharmacol Rev. 2003, 55 (2): 241-269.PubMed Asadullah K, Sterry W, Volk HD: Interleukin-10 therapy–review of a new approach. Pharmacol Rev. 2003, 55 (2): 241-269.PubMed
126.
go back to reference Csiszar A, Wang M, Lakatta EG, Ungvari Z: Inflammation and endothelial dysfunction during aging: role of NF-kappaB. J Appl Physiol (1985). 2008, 105 (4): 1333-1341. Csiszar A, Wang M, Lakatta EG, Ungvari Z: Inflammation and endothelial dysfunction during aging: role of NF-kappaB. J Appl Physiol (1985). 2008, 105 (4): 1333-1341.
127.
go back to reference Marchesi C, Paradis P, Schiffrin EL: Role of the renin-angiotensin system in vascular inflammation. Trends Pharmacol Sci. 2008, 29 (7): 367-374.PubMed Marchesi C, Paradis P, Schiffrin EL: Role of the renin-angiotensin system in vascular inflammation. Trends Pharmacol Sci. 2008, 29 (7): 367-374.PubMed
128.
go back to reference Huang X, Gong R, Li X, Virtue A, Yang F, Yang IH, Tran AH, Yang XF, Wang H: Identification of novel pretranslational regulatory mechanisms for NF-kappaB activation. J Biol Chem. 2013, 288 (22): 15628-15640.PubMedCentralPubMed Huang X, Gong R, Li X, Virtue A, Yang F, Yang IH, Tran AH, Yang XF, Wang H: Identification of novel pretranslational regulatory mechanisms for NF-kappaB activation. J Biol Chem. 2013, 288 (22): 15628-15640.PubMedCentralPubMed
129.
go back to reference Seitz M, Loetscher P, Dewald B, Towbin H, Gallati H, Baggiolini M: Interleukin-10 differentially regulates cytokine inhibitor and chemokine release from blood mononuclear cells and fibroblasts. Eur J Immunol. 1995, 25 (4): 1129-1132.PubMed Seitz M, Loetscher P, Dewald B, Towbin H, Gallati H, Baggiolini M: Interleukin-10 differentially regulates cytokine inhibitor and chemokine release from blood mononuclear cells and fibroblasts. Eur J Immunol. 1995, 25 (4): 1129-1132.PubMed
130.
go back to reference Zemse SM, Chiao CW, Hilgers RH, Webb RC: Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-alpha on the endothelium of murine aorta. Am J Physiol Heart Circ Physiol. 2010, 299 (4): H1160-H1167.PubMedCentralPubMed Zemse SM, Chiao CW, Hilgers RH, Webb RC: Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-alpha on the endothelium of murine aorta. Am J Physiol Heart Circ Physiol. 2010, 299 (4): H1160-H1167.PubMedCentralPubMed
131.
go back to reference Riley JK, Takeda K, Akira S, Schreiber RD: Interleukin-10 receptor signaling through the JAK-STAT pathway. Requirement for two distinct receptor-derived signals for anti-inflammatory action. J Biol Chem. 1999, 274 (23): 16513-16521.PubMed Riley JK, Takeda K, Akira S, Schreiber RD: Interleukin-10 receptor signaling through the JAK-STAT pathway. Requirement for two distinct receptor-derived signals for anti-inflammatory action. J Biol Chem. 1999, 274 (23): 16513-16521.PubMed
132.
go back to reference Cattaruzza M, Slodowski W, Stojakovic M, Krzesz R, Hecker M: Interleukin-10 induction of nitric-oxide synthase expression attenuates CD40-mediated interleukin-12 synthesis in human endothelial cells. J Biol Chem. 2003, 278 (39): 37874-37880.PubMed Cattaruzza M, Slodowski W, Stojakovic M, Krzesz R, Hecker M: Interleukin-10 induction of nitric-oxide synthase expression attenuates CD40-mediated interleukin-12 synthesis in human endothelial cells. J Biol Chem. 2003, 278 (39): 37874-37880.PubMed
133.
go back to reference Wehinger J, Gouilleux F, Groner B, Finke J, Mertelsmann R, Weber-Nordt RM: IL-10 induces DNA binding activity of three STAT proteins (Stat1, Stat3, and Stat5) and their distinct combinatorial assembly in the promoters of selected genes. FEBS Lett. 1996, 394 (3): 365-370.PubMed Wehinger J, Gouilleux F, Groner B, Finke J, Mertelsmann R, Weber-Nordt RM: IL-10 induces DNA binding activity of three STAT proteins (Stat1, Stat3, and Stat5) and their distinct combinatorial assembly in the promoters of selected genes. FEBS Lett. 1996, 394 (3): 365-370.PubMed
134.
go back to reference Finbloom DS, Winestock KD: IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol. 1995, 155 (3): 1079-1090.PubMed Finbloom DS, Winestock KD: IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol. 1995, 155 (3): 1079-1090.PubMed
135.
go back to reference Pattison MJ, Mackenzie KF, Arthur JS: Inhibition of JAKs in macrophages increases lipopolysaccharide-induced cytokine production by blocking IL-10-mediated feedback. J Immunol. 2012, 189 (6): 2784-2792.PubMedCentralPubMed Pattison MJ, Mackenzie KF, Arthur JS: Inhibition of JAKs in macrophages increases lipopolysaccharide-induced cytokine production by blocking IL-10-mediated feedback. J Immunol. 2012, 189 (6): 2784-2792.PubMedCentralPubMed
136.
go back to reference Jojima T, Suzuki K, Hirama N, Uchida K, Hattori Y: Glimepiride upregulates eNOS activity and inhibits cytokine-induced NF-kappaB activation through a phosphoinoside 3-kinase-Akt-dependent pathway. Diabetes Obes Metab. 2009, 11 (2): 143-149.PubMed Jojima T, Suzuki K, Hirama N, Uchida K, Hattori Y: Glimepiride upregulates eNOS activity and inhibits cytokine-induced NF-kappaB activation through a phosphoinoside 3-kinase-Akt-dependent pathway. Diabetes Obes Metab. 2009, 11 (2): 143-149.PubMed
137.
go back to reference D'Angelo G, Adam LP: Inhibition of ERK attenuates force development by lowering myosin light chain phosphorylation. Am J Physiol Heart Circ Physiol. 2002, 282 (2): H602-H610.PubMed D'Angelo G, Adam LP: Inhibition of ERK attenuates force development by lowering myosin light chain phosphorylation. Am J Physiol Heart Circ Physiol. 2002, 282 (2): H602-H610.PubMed
138.
go back to reference Stumpf C, Lehner C, Yilmaz A, Daniel WG, Garlichs CD: Decrease of serum levels of the anti-inflammatory cytokine interleukin-10 in patients with advanced chronic heart failure. Clin Sci (Lond). 2003, 105 (1): 45-50. Stumpf C, Lehner C, Yilmaz A, Daniel WG, Garlichs CD: Decrease of serum levels of the anti-inflammatory cytokine interleukin-10 in patients with advanced chronic heart failure. Clin Sci (Lond). 2003, 105 (1): 45-50.
139.
go back to reference Suttles J, Milhorn DM, Miller RW, Poe JC, Wahl LM, Stout RD: CD40 signaling of monocyte inflammatory cytokine synthesis through an ERK1/2-dependent pathway. A target of interleukin (il)-4 and il-10 anti-inflammatory action. J Biol Chem. 1999, 274 (9): 5835-5842.PubMed Suttles J, Milhorn DM, Miller RW, Poe JC, Wahl LM, Stout RD: CD40 signaling of monocyte inflammatory cytokine synthesis through an ERK1/2-dependent pathway. A target of interleukin (il)-4 and il-10 anti-inflammatory action. J Biol Chem. 1999, 274 (9): 5835-5842.PubMed
140.
go back to reference Giachini FR, Zemse SM, Carneiro FS, Lima VV, Carneiro ZN, Callera GE, Ergul A, Webb RC, Tostes RC: Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway. Am J Physiol Heart Circ Physiol. 2009, 296 (2): H489-H496.PubMedCentralPubMed Giachini FR, Zemse SM, Carneiro FS, Lima VV, Carneiro ZN, Callera GE, Ergul A, Webb RC, Tostes RC: Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway. Am J Physiol Heart Circ Physiol. 2009, 296 (2): H489-H496.PubMedCentralPubMed
141.
go back to reference Noh KT, Son KH, Jung ID, Kang HK, Hwang SA, Lee WS, You JC, Park YM: Protein kinase C delta (PKCdelta)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade regulates glycogen synthase kinase-3 (GSK-3) inhibition-mediated interleukin-10 (IL-10) expression in lipopolysaccharide (LPS)-induced endotoxemia. J Biol Chem. 2012, 287 (17): 14226-14233.PubMedCentralPubMed Noh KT, Son KH, Jung ID, Kang HK, Hwang SA, Lee WS, You JC, Park YM: Protein kinase C delta (PKCdelta)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade regulates glycogen synthase kinase-3 (GSK-3) inhibition-mediated interleukin-10 (IL-10) expression in lipopolysaccharide (LPS)-induced endotoxemia. J Biol Chem. 2012, 287 (17): 14226-14233.PubMedCentralPubMed
142.
go back to reference Williams L, Bradley L, Smith A, Foxwell B: Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol. 2004, 172 (1): 567-576.PubMed Williams L, Bradley L, Smith A, Foxwell B: Signal transducer and activator of transcription 3 is the dominant mediator of the anti-inflammatory effects of IL-10 in human macrophages. J Immunol. 2004, 172 (1): 567-576.PubMed
143.
go back to reference Lang R, Patel D, Morris JJ, Rutschman RL, Murray PJ: Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol. 2002, 169 (5): 2253-2263.PubMed Lang R, Patel D, Morris JJ, Rutschman RL, Murray PJ: Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol. 2002, 169 (5): 2253-2263.PubMed
144.
go back to reference Antoniv TT, Ivashkiv LB: Interleukin-10-induced gene expression and suppressive function are selectively modulated by the PI3K-Akt-GSK3 pathway. Immunology. 2011, 132 (4): 567-577.PubMedCentralPubMed Antoniv TT, Ivashkiv LB: Interleukin-10-induced gene expression and suppressive function are selectively modulated by the PI3K-Akt-GSK3 pathway. Immunology. 2011, 132 (4): 567-577.PubMedCentralPubMed
145.
go back to reference Pepper MS: Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev. 1997, 8 (1): 21-43.PubMed Pepper MS: Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev. 1997, 8 (1): 21-43.PubMed
146.
go back to reference Massague J: The transforming growth factor-beta family. Annu Rev Cell Biol. 1990, 6: 597-641.PubMed Massague J: The transforming growth factor-beta family. Annu Rev Cell Biol. 1990, 6: 597-641.PubMed
147.
go back to reference Roberts AB: Molecular and cell biology of TGF-beta. Miner Electrolyte Metab. 1998, 24 (2–3): 111-119.PubMed Roberts AB: Molecular and cell biology of TGF-beta. Miner Electrolyte Metab. 1998, 24 (2–3): 111-119.PubMed
148.
go back to reference Morello JP, Plamondon J, Meyrick B, Hoover R, O'Connor-McCourt MD: Transforming growth factor-beta receptor expression on endothelial cells: heterogeneity of type III receptor expression. J Cell Physiol. 1995, 165 (1): 201-211.PubMed Morello JP, Plamondon J, Meyrick B, Hoover R, O'Connor-McCourt MD: Transforming growth factor-beta receptor expression on endothelial cells: heterogeneity of type III receptor expression. J Cell Physiol. 1995, 165 (1): 201-211.PubMed
149.
go back to reference Saura M, Zaragoza C, Cao W, Bao C, Rodriguez-Puyol M, Rodriguez-Puyol D, Lowenstein CJ: Smad2 mediates transforming growth factor-beta induction of endothelial nitric oxide synthase expression. Circ Res. 2002, 91 (9): 806-813.PubMed Saura M, Zaragoza C, Cao W, Bao C, Rodriguez-Puyol M, Rodriguez-Puyol D, Lowenstein CJ: Smad2 mediates transforming growth factor-beta induction of endothelial nitric oxide synthase expression. Circ Res. 2002, 91 (9): 806-813.PubMed
150.
go back to reference Vasquez R, Farias M, Vega JL, Martin RS, Vecchiola A, Casanello P, Sobrevia L: D-glucose stimulation of L-arginine transport and nitric oxide synthesis results from activation of mitogen-activated protein kinases p42/44 and Smad2 requiring functional type II TGF-beta receptors in human umbilical vein endothelium. J Cell Physiol. 2007, 212 (3): 626-632.PubMed Vasquez R, Farias M, Vega JL, Martin RS, Vecchiola A, Casanello P, Sobrevia L: D-glucose stimulation of L-arginine transport and nitric oxide synthesis results from activation of mitogen-activated protein kinases p42/44 and Smad2 requiring functional type II TGF-beta receptors in human umbilical vein endothelium. J Cell Physiol. 2007, 212 (3): 626-632.PubMed
151.
go back to reference Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS: Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986, 163 (5): 1037-1050.PubMed Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS: Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986, 163 (5): 1037-1050.PubMed
152.
go back to reference Saura M, Zaragoza C, Herranz B, Griera M, Diez-Marques L, Rodriguez-Puyol D, Rodriguez-Puyol M: Nitric oxide regulates transforming growth factor-beta signaling in endothelial cells. Circ Res. 2005, 97 (11): 1115-1123.PubMed Saura M, Zaragoza C, Herranz B, Griera M, Diez-Marques L, Rodriguez-Puyol D, Rodriguez-Puyol M: Nitric oxide regulates transforming growth factor-beta signaling in endothelial cells. Circ Res. 2005, 97 (11): 1115-1123.PubMed
153.
go back to reference Walshe TE, dela Paz NG, D’Amore PA: The role of shear-induced transforming growth factor-beta signaling in the endothelium. Arterioscler Thromb Vasc Biol. 2013, 33 (11): 2608-2617.PubMedCentralPubMed Walshe TE, dela Paz NG, D’Amore PA: The role of shear-induced transforming growth factor-beta signaling in the endothelium. Arterioscler Thromb Vasc Biol. 2013, 33 (11): 2608-2617.PubMedCentralPubMed
154.
go back to reference Ying WZ, Aaron KJ, Sanders PW: Transforming growth factor-beta regulates endothelial function during high salt intake in rats. Hypertension. 2013, 62 (5): 951-956.PubMedCentralPubMed Ying WZ, Aaron KJ, Sanders PW: Transforming growth factor-beta regulates endothelial function during high salt intake in rats. Hypertension. 2013, 62 (5): 951-956.PubMedCentralPubMed
155.
go back to reference Letterio JJ, Roberts AB: Regulation of immune responses by TGF-beta. Annu Rev Immunol. 1998, 16: 137-161.PubMed Letterio JJ, Roberts AB: Regulation of immune responses by TGF-beta. Annu Rev Immunol. 1998, 16: 137-161.PubMed
156.
go back to reference Li MO, Wan YY, Flavell RA: T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity. 2007, 26 (5): 579-591.PubMed Li MO, Wan YY, Flavell RA: T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity. 2007, 26 (5): 579-591.PubMed
157.
go back to reference Pastrana JL, Sha X, Virtue A, Mai J, Cueto R, Lee IA, Wang H, Yang XF: Regulatory T cells and Atherosclerosis. J Clin Exp Cardiolog. 2012, 2012 (Suppl 12): 2-PubMed Pastrana JL, Sha X, Virtue A, Mai J, Cueto R, Lee IA, Wang H, Yang XF: Regulatory T cells and Atherosclerosis. J Clin Exp Cardiolog. 2012, 2012 (Suppl 12): 2-PubMed
158.
go back to reference Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA: IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol. 2010, 11 (11): 1014-1022.PubMedCentralPubMed Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA: IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol. 2010, 11 (11): 1014-1022.PubMedCentralPubMed
159.
go back to reference Miller AM: Role of IL-33 in inflammation and disease. J Inflamm (Lond). 2011, 8 (1): 22- Miller AM: Role of IL-33 in inflammation and disease. J Inflamm (Lond). 2011, 8 (1): 22-
160.
go back to reference Miller AM, Xu D, Asquith DL, Denby L, Li Y, Sattar N, Baker AH, McInnes IB, Liew FY: IL-33 reduces the development of atherosclerosis. J Exp Med. 2008, 205 (2): 339-346.PubMedCentralPubMed Miller AM, Xu D, Asquith DL, Denby L, Li Y, Sattar N, Baker AH, McInnes IB, Liew FY: IL-33 reduces the development of atherosclerosis. J Exp Med. 2008, 205 (2): 339-346.PubMedCentralPubMed
161.
go back to reference Miller AM, Asquith DL, Hueber AJ, Anderson LA, Holmes WM, McKenzie AN, Xu D, Sattar N, McInnes IB, Liew FY: Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res. 2010, 107 (5): 650-658.PubMedCentralPubMed Miller AM, Asquith DL, Hueber AJ, Anderson LA, Holmes WM, McKenzie AN, Xu D, Sattar N, McInnes IB, Liew FY: Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res. 2010, 107 (5): 650-658.PubMedCentralPubMed
162.
go back to reference Moussion C, Ortega N, Girard JP: The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'?. PLoS One. 2008, 3 (10): e3331-PubMedCentralPubMed Moussion C, Ortega N, Girard JP: The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'?. PLoS One. 2008, 3 (10): e3331-PubMedCentralPubMed
163.
go back to reference Grehan JF, Levay-Young BK, Fogelson JL, Francois-Bongarcon V, Benson BA, Dalmasso AP: IL-4 and IL-13 induce protection of porcine endothelial cells from killing by human complement and from apoptosis through activation of a phosphatidylinositide 3-kinase/Akt pathway. J Immunol. 2005, 175 (3): 1903-1910.PubMed Grehan JF, Levay-Young BK, Fogelson JL, Francois-Bongarcon V, Benson BA, Dalmasso AP: IL-4 and IL-13 induce protection of porcine endothelial cells from killing by human complement and from apoptosis through activation of a phosphatidylinositide 3-kinase/Akt pathway. J Immunol. 2005, 175 (3): 1903-1910.PubMed
164.
go back to reference Dalmasso AP, Goldish D, Benson BA, Tsai AK, Wasiluk KR, Vercellotti GM: Interleukin-4 induces up-regulation of endothelial cell claudin-5 through activation of FoxO1: role in protection from complement-mediated injury. J Biol Chem. 2014, 289 (2): 838-847.PubMedCentralPubMed Dalmasso AP, Goldish D, Benson BA, Tsai AK, Wasiluk KR, Vercellotti GM: Interleukin-4 induces up-regulation of endothelial cell claudin-5 through activation of FoxO1: role in protection from complement-mediated injury. J Biol Chem. 2014, 289 (2): 838-847.PubMedCentralPubMed
165.
go back to reference Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS, Vignali DA: The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 2007, 450 (7169): 566-569.PubMed Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS, Vignali DA: The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 2007, 450 (7169): 566-569.PubMed
166.
go back to reference Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, Wingfield PT, Kim SH, Egwuagu CE: Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med. 2014, 20 (6): 633-641.PubMedCentralPubMed Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, Wingfield PT, Kim SH, Egwuagu CE: Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med. 2014, 20 (6): 633-641.PubMedCentralPubMed
167.
go back to reference Shen P, Roch T, Lampropoulou V, O'Connor RA, Stervbo U, Hilgenberg E, Ries S, Dang VD, Jaimes Y, Daridon C, Li R, Jouneau L, Boudinot P, Wilantri S, Sakwa I, Miyazaki Y, Leech MD, McPherson RC, Wirtz S, Neurath M, Hoehlig K, Meinl E, Grützkau A, Grün JR, Horn K, Kühl AA, Dörner T, Bar-Or A, Kaufmann SH, Anderton SM: IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature. 2014, 507 (7492): 366-370.PubMedCentralPubMed Shen P, Roch T, Lampropoulou V, O'Connor RA, Stervbo U, Hilgenberg E, Ries S, Dang VD, Jaimes Y, Daridon C, Li R, Jouneau L, Boudinot P, Wilantri S, Sakwa I, Miyazaki Y, Leech MD, McPherson RC, Wirtz S, Neurath M, Hoehlig K, Meinl E, Grützkau A, Grün JR, Horn K, Kühl AA, Dörner T, Bar-Or A, Kaufmann SH, Anderton SM: IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature. 2014, 507 (7492): 366-370.PubMedCentralPubMed
168.
go back to reference Li X, Mai J, Virtue A, Yin Y, Gong R, Sha X, Gutchigian S, Frisch A, Hodge I, Jiang X, Wang H, Yang XF: IL-35 is a novel responsive anti-inflammatory cytokine–a new system of categorizing anti-inflammatory cytokines. PLoS One. 2012, 7 (3): e33628-PubMedCentralPubMed Li X, Mai J, Virtue A, Yin Y, Gong R, Sha X, Gutchigian S, Frisch A, Hodge I, Jiang X, Wang H, Yang XF: IL-35 is a novel responsive anti-inflammatory cytokine–a new system of categorizing anti-inflammatory cytokines. PLoS One. 2012, 7 (3): e33628-PubMedCentralPubMed
169.
go back to reference Virtue A, Wang H, Yang XF: MicroRNAs and toll-like receptor/interleukin-1 receptor signaling. J Hematol Oncol. 2012, 5: 66-PubMedCentralPubMed Virtue A, Wang H, Yang XF: MicroRNAs and toll-like receptor/interleukin-1 receptor signaling. J Hematol Oncol. 2012, 5: 66-PubMedCentralPubMed
170.
go back to reference Virtue A, Mai J, Yin Y, Meng S, Tran T, Jiang X, Wang H, Yang XF: Structural evidence of anti-atherogenic microRNAs. Front Biosci (Landmark Ed). 2011, 16: 3133-3145. Virtue A, Mai J, Yin Y, Meng S, Tran T, Jiang X, Wang H, Yang XF: Structural evidence of anti-atherogenic microRNAs. Front Biosci (Landmark Ed). 2011, 16: 3133-3145.
171.
go back to reference Taganov KD, Boldin MP, Chang KJ, Baltimore D: NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006, 103 (33): 12481-12486.PubMedCentralPubMed Taganov KD, Boldin MP, Chang KJ, Baltimore D: NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006, 103 (33): 12481-12486.PubMedCentralPubMed
172.
go back to reference Bhaumik D, Patil CK, Campisi J: MicroRNAs: an important player in maintaining a balance between inflammation and tumor suppression. Cell Cycle. 2009, 8 (12): 1822-PubMed Bhaumik D, Patil CK, Campisi J: MicroRNAs: an important player in maintaining a balance between inflammation and tumor suppression. Cell Cycle. 2009, 8 (12): 1822-PubMed
173.
go back to reference Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay MA: Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory response in human lung alveolar epithelial cells. J Immunol. 2008, 180 (8): 5689-5698.PubMedCentralPubMed Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay MA: Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory response in human lung alveolar epithelial cells. J Immunol. 2008, 180 (8): 5689-5698.PubMedCentralPubMed
174.
go back to reference Xiao B, Liu Z, Li BS, Tang B, Li W, Guo G, Shi Y, Wang F, Wu Y, Tong WD, Guo H, Mao XH, Zou QM: Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response. J Infect Dis. 2009, 200 (6): 916-925.PubMed Xiao B, Liu Z, Li BS, Tang B, Li W, Guo G, Shi Y, Wang F, Wu Y, Tong WD, Guo H, Mao XH, Zou QM: Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response. J Infect Dis. 2009, 200 (6): 916-925.PubMed
175.
go back to reference Worm J, Stenvang J, Petri A, Frederiksen KS, Obad S, Elmen J, Hedtjarn M, Straarup EM, Hansen JB, Kauppinen S: Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of c/ebp Beta and down-regulation of G-CSF. Nucleic Acids Res. 2009, 37 (17): 5784-5792.PubMedCentralPubMed Worm J, Stenvang J, Petri A, Frederiksen KS, Obad S, Elmen J, Hedtjarn M, Straarup EM, Hansen JB, Kauppinen S: Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of c/ebp Beta and down-regulation of G-CSF. Nucleic Acids Res. 2009, 37 (17): 5784-5792.PubMedCentralPubMed
176.
go back to reference Matsui J, Wakabayashi T, Asada M, Yoshimatsu K, Okada M: Stem cell factor/c-kit signaling promotes the survival, migration, and capillary tube formation of human umbilical vein endothelial cells. J Biol Chem. 2004, 279 (18): 18600-18607.PubMed Matsui J, Wakabayashi T, Asada M, Yoshimatsu K, Okada M: Stem cell factor/c-kit signaling promotes the survival, migration, and capillary tube formation of human umbilical vein endothelial cells. J Biol Chem. 2004, 279 (18): 18600-18607.PubMed
177.
go back to reference Suarez Y, Wang C, Manes TD, Pober JS: Cutting edge: TNF-induced microRNAs regulate TNF-induced expression of E-selectin and intercellular adhesion molecule-1 on human endothelial cells: feedback control of inflammation. J Immunol. 2010, 184 (1): 21-25.PubMedCentralPubMed Suarez Y, Wang C, Manes TD, Pober JS: Cutting edge: TNF-induced microRNAs regulate TNF-induced expression of E-selectin and intercellular adhesion molecule-1 on human endothelial cells: feedback control of inflammation. J Immunol. 2010, 184 (1): 21-25.PubMedCentralPubMed
178.
go back to reference Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ: MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A. 2008, 105 (5): 1516-1521.PubMedCentralPubMed Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ: MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A. 2008, 105 (5): 1516-1521.PubMedCentralPubMed
179.
go back to reference Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, Hunninghake GM, Vera MP, Blackwell TS, Baron RM, Feinberg MW: MicroRNA-181b regulates NF-kappaB-mediated vascular inflammation. J Clin Invest. 2012, 122 (6): 1973-1990.PubMedCentralPubMed Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, Hunninghake GM, Vera MP, Blackwell TS, Baron RM, Feinberg MW: MicroRNA-181b regulates NF-kappaB-mediated vascular inflammation. J Clin Invest. 2012, 122 (6): 1973-1990.PubMedCentralPubMed
180.
go back to reference Fang Y, Shi C, Manduchi E, Civelek M, Davies PF: MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci U S A. 2010, 107 (30): 13450-13455.PubMedCentralPubMed Fang Y, Shi C, Manduchi E, Civelek M, Davies PF: MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci U S A. 2010, 107 (30): 13450-13455.PubMedCentralPubMed
181.
go back to reference Suarez Y, Fernandez-Hernando C, Pober JS, Sessa WC: Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 2007, 100 (8): 1164-1173.PubMed Suarez Y, Fernandez-Hernando C, Pober JS, Sessa WC: Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 2007, 100 (8): 1164-1173.PubMed
182.
go back to reference Hagiwara S, McClelland A, Kantharidis P: MicroRNA in Diabetic Nephropathy: Renin Angiotensin, AGE/RAGE, and Oxidative Stress Pathway. J Diabetes Res. 2013, 2013: 173783-PubMedCentralPubMed Hagiwara S, McClelland A, Kantharidis P: MicroRNA in Diabetic Nephropathy: Renin Angiotensin, AGE/RAGE, and Oxidative Stress Pathway. J Diabetes Res. 2013, 2013: 173783-PubMedCentralPubMed
183.
go back to reference Sun HX, Zeng DY, Li RT, Pang RP, Yang H, Hu YL, Zhang Q, Jiang Y, Huang LY, Tang YB, Yan GJ, Zhou JG: Essential role of microRNA-155 in regulating endothelium-dependent vasorelaxation by targeting endothelial nitric oxide synthase. Hypertension. 2012, 60 (6): 1407-1414.PubMed Sun HX, Zeng DY, Li RT, Pang RP, Yang H, Hu YL, Zhang Q, Jiang Y, Huang LY, Tang YB, Yan GJ, Zhou JG: Essential role of microRNA-155 in regulating endothelium-dependent vasorelaxation by targeting endothelial nitric oxide synthase. Hypertension. 2012, 60 (6): 1407-1414.PubMed
184.
go back to reference Li D, Yang P, Xiong Q, Song X, Yang X, Liu L, Yuan W, Rui YC: MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells. J Hypertens. 2010, 28 (8): 1646-1654.PubMed Li D, Yang P, Xiong Q, Song X, Yang X, Liu L, Yuan W, Rui YC: MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells. J Hypertens. 2010, 28 (8): 1646-1654.PubMed
Metadata
Title
Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction- a novel mechanism for maintaining vascular function
Authors
Ying Shao
Zhongjian Cheng
Xinyuan Li
Valeria Chernaya
Hong Wang
Xiao-feng Yang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2014
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-014-0080-6

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