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Published in: BMC Cardiovascular Disorders 1/2010

Open Access 01-12-2010 | Research article

Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction

Authors: Andreas Stein, Martina Knödler, Markus Makowski, Sandra Kühnel, Stefan Nekolla, Alexandra Keithahn, Eliane Weidl, Philip Groha, Maren Schürmann, Atti Saraste, Rene Botnar, Robert AJ Oostendorp, Ilka Ott

Published in: BMC Cardiovascular Disorders | Issue 1/2010

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Abstract

Background

Expanded endothelial progenitor cells (eEPC) improve global left ventricular function in experimental myocardial infarction (MI). Erythropoietin beta (EPO) applied together with eEPC may improve regional myocardial function even further by anti-apoptotic and cardioprotective effects. Aim of this study was to evaluate intramyocardial application of eEPCs and EPO as compared to eEPCs or EPO alone in experimental MI.

Methods and Results

In vitro experiments revealed that EPO dosed-dependently decreased eEPC and leukocyte apoptosis. Moreover, in the presence of EPO mRNA expression in eEPC of proangiogenic and proinflammatory mediators measured by TaqMan PCR was enhanced. Experimental MI was induced by ligation and reperfusion of the left anterior descending coronary artery of nude rats (n = 8-9). After myocardial transplantation of eEPC and EPO CD68+ leukocyte count and vessel density were enhanced in the border zone of the infarct area. Moreover, apoptosis of transplanted CD31 + TUNEL + eEPC was decreased as compared to transplantation of eEPCs alone. Regional wall motion of the left ventricle was measured using Magnetic Resonance Imaging. After injection of eEPC in the presence of EPO regional wall motion significantly improved as compared to injection of eEPCs or EPO alone.

Conclusion

Intramyocardial transplantation of eEPC in the presence of EPO during experimental MI improves regional wall motion. This was associated with an increased local inflammation, vasculogenesis and survival of the transplanted cells. Local application of EPO in addition to cell therapy may prove beneficial in myocardial remodeling.
Appendix
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Literature
1.
go back to reference Leone AM, Rutella S, Bonanno G, Abbate A, Rebuzzi AG, Giovannini S, Lombardi M, Galiuto L, Liuzzo G, Andreotti F, et al: Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function. Eur Heart J. 2005, 26 (12): 1196-1204. 10.1093/eurheartj/ehi164.CrossRefPubMed Leone AM, Rutella S, Bonanno G, Abbate A, Rebuzzi AG, Giovannini S, Lombardi M, Galiuto L, Liuzzo G, Andreotti F, et al: Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function. Eur Heart J. 2005, 26 (12): 1196-1204. 10.1093/eurheartj/ehi164.CrossRefPubMed
2.
go back to reference Massa M, Rosti V, Ferrario M, Campanelli R, Ramajoli I, Rosso R, De Ferrari GM, Ferlini M, Goffredo L, Bertoletti A, et al: Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood. 2005, 105 (1): 199-206. 10.1182/blood-2004-05-1831.CrossRefPubMed Massa M, Rosti V, Ferrario M, Campanelli R, Ramajoli I, Rosso R, De Ferrari GM, Ferlini M, Goffredo L, Bertoletti A, et al: Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood. 2005, 105 (1): 199-206. 10.1182/blood-2004-05-1831.CrossRefPubMed
3.
go back to reference Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Ochala A, Ratajczak MZ: Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004, 110 (20): 3213-3220. 10.1161/01.CIR.0000147609.39780.02.CrossRefPubMed Wojakowski W, Tendera M, Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Ochala A, Ratajczak MZ: Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004, 110 (20): 3213-3220. 10.1161/01.CIR.0000147609.39780.02.CrossRefPubMed
4.
go back to reference Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Salio M, Cerami A, Brines M: Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA. 2003, 100 (8): 4802-4806. 10.1073/pnas.0630444100.CrossRefPubMedPubMedCentral Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Salio M, Cerami A, Brines M: Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA. 2003, 100 (8): 4802-4806. 10.1073/pnas.0630444100.CrossRefPubMedPubMedCentral
5.
go back to reference Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P: Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA. 2001, 98 (18): 10344-10349. 10.1073/pnas.181177898.CrossRefPubMedPubMedCentral Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P: Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA. 2001, 98 (18): 10344-10349. 10.1073/pnas.181177898.CrossRefPubMedPubMedCentral
6.
go back to reference Ott I, Keller U, Knoedler M, Gotze KS, Doss K, Fischer P, Urlbauer K, Debus G, von Bubnoff N, Rudelius M, et al: Endothelial-like cells expanded from CD34+ blood cells improve left ventricular function after experimental myocardial infarction. Faseb J. 2005, 19 (8): 992-994.PubMed Ott I, Keller U, Knoedler M, Gotze KS, Doss K, Fischer P, Urlbauer K, Debus G, von Bubnoff N, Rudelius M, et al: Endothelial-like cells expanded from CD34+ blood cells improve left ventricular function after experimental myocardial infarction. Faseb J. 2005, 19 (8): 992-994.PubMed
7.
go back to reference Dawn B, Bolli R: Adult bone marrow-derived cells: regenerative potential, plasticity, and tissue commitment. Basic Res Cardiol. 2005, 100 (6): 494-503. 10.1007/s00395-005-0552-5.CrossRefPubMedPubMedCentral Dawn B, Bolli R: Adult bone marrow-derived cells: regenerative potential, plasticity, and tissue commitment. Basic Res Cardiol. 2005, 100 (6): 494-503. 10.1007/s00395-005-0552-5.CrossRefPubMedPubMedCentral
8.
go back to reference Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B: Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007, 167 (10): 989-997. 10.1001/archinte.167.10.989.CrossRefPubMed Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B: Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007, 167 (10): 989-997. 10.1001/archinte.167.10.989.CrossRefPubMed
9.
go back to reference Belonje AM, Westenbrink BD, Voors AA, von Haehling S, Ponikowski P, Anker SD, van Veldhuisen DJ, Dickstein K: Erythropoietin levels in heart failure after an acute myocardial infarction: determinants, prognostic value, and the effects of captopril versus losartan. Am Heart J. 2009, 157 (1): 91-96. 10.1016/j.ahj.2008.08.020.CrossRefPubMed Belonje AM, Westenbrink BD, Voors AA, von Haehling S, Ponikowski P, Anker SD, van Veldhuisen DJ, Dickstein K: Erythropoietin levels in heart failure after an acute myocardial infarction: determinants, prognostic value, and the effects of captopril versus losartan. Am Heart J. 2009, 157 (1): 91-96. 10.1016/j.ahj.2008.08.020.CrossRefPubMed
10.
go back to reference van der Meer P, Lipsic E, Henning RH, de Boer RA, Suurmeijer AJ, van Veldhuisen DJ, van Gilst WH: Erythropoietin improves left ventricular function and coronary flow in an experimental model of ischemia-reperfusion injury. Eur J Heart Fail. 2004, 6 (7): 853-859.CrossRefPubMed van der Meer P, Lipsic E, Henning RH, de Boer RA, Suurmeijer AJ, van Veldhuisen DJ, van Gilst WH: Erythropoietin improves left ventricular function and coronary flow in an experimental model of ischemia-reperfusion injury. Eur J Heart Fail. 2004, 6 (7): 853-859.CrossRefPubMed
11.
go back to reference Sterin-Borda L, Barcelo AC, Bozzini CE: Erythropoietin improves cardiac contractility in post-hypoxic mice. Br J Haematol. 2003, 121 (1): 180-186. 10.1046/j.1365-2141.2003.04239.x.CrossRefPubMed Sterin-Borda L, Barcelo AC, Bozzini CE: Erythropoietin improves cardiac contractility in post-hypoxic mice. Br J Haematol. 2003, 121 (1): 180-186. 10.1046/j.1365-2141.2003.04239.x.CrossRefPubMed
12.
go back to reference Moon C, Krawczyk M, Ahn D, Ahmet I, Paik D, Lakatta EG, Talan MI: Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci USA. 2003, 100 (20): 11612-11617. 10.1073/pnas.1930406100.CrossRefPubMedPubMedCentral Moon C, Krawczyk M, Ahn D, Ahmet I, Paik D, Lakatta EG, Talan MI: Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci USA. 2003, 100 (20): 11612-11617. 10.1073/pnas.1930406100.CrossRefPubMedPubMedCentral
14.
go back to reference Katavetin P, Inagi R, Miyata T, Shao J, Sassa R, Adler S, Eto N, Kato H, Fujita T, Nangaku M: Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress. Biochem Biophys Res Commun. 2007, 359 (4): 928-934. 10.1016/j.bbrc.2007.05.207.CrossRefPubMed Katavetin P, Inagi R, Miyata T, Shao J, Sassa R, Adler S, Eto N, Kato H, Fujita T, Nangaku M: Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress. Biochem Biophys Res Commun. 2007, 359 (4): 928-934. 10.1016/j.bbrc.2007.05.207.CrossRefPubMed
15.
go back to reference Anagnostou A, Liu Z, Steiner M, Chin K, Lee ES, Kessimian N, Noguchi CT: Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci USA. 1994, 91 (9): 3974-3978. 10.1073/pnas.91.9.3974.CrossRefPubMedPubMedCentral Anagnostou A, Liu Z, Steiner M, Chin K, Lee ES, Kessimian N, Noguchi CT: Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci USA. 1994, 91 (9): 3974-3978. 10.1073/pnas.91.9.3974.CrossRefPubMedPubMedCentral
16.
go back to reference Masuda S, Nagao M, Takahata K, Konishi Y, Gallyas F, Tabira T, Sasaki R: Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells. J Biol Chem. 1993, 268 (15): 11208-11216.PubMed Masuda S, Nagao M, Takahata K, Konishi Y, Gallyas F, Tabira T, Sasaki R: Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells. J Biol Chem. 1993, 268 (15): 11208-11216.PubMed
17.
go back to reference Wu H, Lee SH, Gao J, Liu X, Iruela-Arispe ML: Inactivation of erythropoietin leads to defects in cardiac morphogenesis. Development. 1999, 126 (16): 3597-3605.PubMed Wu H, Lee SH, Gao J, Liu X, Iruela-Arispe ML: Inactivation of erythropoietin leads to defects in cardiac morphogenesis. Development. 1999, 126 (16): 3597-3605.PubMed
18.
go back to reference Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN: JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 1993, 74 (2): 227-236. 10.1016/0092-8674(93)90414-L.CrossRefPubMed Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN: JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 1993, 74 (2): 227-236. 10.1016/0092-8674(93)90414-L.CrossRefPubMed
19.
go back to reference Bao H, Jacobs-Helber SM, Lawson AE, Penta K, Wickrema A, Sawyer ST: Protein kinase B (c-Akt), phosphatidylinositol 3-kinase, and STAT5 are activated by erythropoietin (EPO) in HCD57 erythroid cells but are constitutively active in an EPO-independent, apoptosis-resistant subclone (HCD57-SREI cells). Blood. 1999, 93 (11): 3757-3773.PubMed Bao H, Jacobs-Helber SM, Lawson AE, Penta K, Wickrema A, Sawyer ST: Protein kinase B (c-Akt), phosphatidylinositol 3-kinase, and STAT5 are activated by erythropoietin (EPO) in HCD57 erythroid cells but are constitutively active in an EPO-independent, apoptosis-resistant subclone (HCD57-SREI cells). Blood. 1999, 93 (11): 3757-3773.PubMed
20.
go back to reference Ashley RA, Dubuque SH, Dvorak B, Woodward SS, Williams SK, Kling PJ: Erythropoietin stimulates vasculogenesis in neonatal rat mesenteric microvascular endothelial cells. Pediatr Res. 2002, 51 (4): 472-478. 10.1203/00006450-200204000-00012.CrossRefPubMed Ashley RA, Dubuque SH, Dvorak B, Woodward SS, Williams SK, Kling PJ: Erythropoietin stimulates vasculogenesis in neonatal rat mesenteric microvascular endothelial cells. Pediatr Res. 2002, 51 (4): 472-478. 10.1203/00006450-200204000-00012.CrossRefPubMed
21.
go back to reference Carlini RG, Reyes AA, Rothstein M: Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney Int. 1995, 47 (3): 740-745. 10.1038/ki.1995.113.CrossRefPubMed Carlini RG, Reyes AA, Rothstein M: Recombinant human erythropoietin stimulates angiogenesis in vitro. Kidney Int. 1995, 47 (3): 740-745. 10.1038/ki.1995.113.CrossRefPubMed
22.
go back to reference Sayan H, Ozacmak VH, Guven A, Aktas RG, Ozacmak ID: Erythropoietin stimulates wound healing and angiogenesis in mice. J Invest Surg. 2006, 19 (3): 163-173. 10.1080/08941930600674694.CrossRefPubMed Sayan H, Ozacmak VH, Guven A, Aktas RG, Ozacmak ID: Erythropoietin stimulates wound healing and angiogenesis in mice. J Invest Surg. 2006, 19 (3): 163-173. 10.1080/08941930600674694.CrossRefPubMed
23.
go back to reference Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S: Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003, 102 (4): 1340-1346. 10.1182/blood-2003-01-0223.CrossRefPubMed Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S: Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003, 102 (4): 1340-1346. 10.1182/blood-2003-01-0223.CrossRefPubMed
24.
go back to reference Brunner S, Winogradow J, Huber BC, Zaruba MM, Fischer R, David R, Assmann G, Herbach N, Wanke R, Mueller-Hoecker J, et al: Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. Faseb J. 2009, 23 (2): 351-361. 10.1096/fj.08-109462.CrossRefPubMed Brunner S, Winogradow J, Huber BC, Zaruba MM, Fischer R, David R, Assmann G, Herbach N, Wanke R, Mueller-Hoecker J, et al: Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. Faseb J. 2009, 23 (2): 351-361. 10.1096/fj.08-109462.CrossRefPubMed
25.
go back to reference Ott I, Neumann FJ, Schomig A: Neutrophil hyper-reactivity after exercise-induced angina pectoris. Coron Artery Dis. 1995, 6 (7): 525-532.PubMed Ott I, Neumann FJ, Schomig A: Neutrophil hyper-reactivity after exercise-induced angina pectoris. Coron Artery Dis. 1995, 6 (7): 525-532.PubMed
26.
go back to reference Li Y, Takemura G, Okada H, Miyata S, Maruyama R, Li L, Higuchi M, Minatoguchi S, Fujiwara T, Fujiwara H: Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res. 2006, 71 (4): 684-694. 10.1016/j.cardiores.2006.06.003.CrossRefPubMed Li Y, Takemura G, Okada H, Miyata S, Maruyama R, Li L, Higuchi M, Minatoguchi S, Fujiwara T, Fujiwara H: Reduction of inflammatory cytokine expression and oxidative damage by erythropoietin in chronic heart failure. Cardiovasc Res. 2006, 71 (4): 684-694. 10.1016/j.cardiores.2006.06.003.CrossRefPubMed
27.
go back to reference Zohlnhofer D, Ott I, Mehilli J, Schomig K, Michalk F, Ibrahim T, Meisetschlager G, von Wedel J, Bollwein H, Seyfarth M, et al: Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial. Jama. 2006, 295 (9): 1003-1010. 10.1001/jama.295.9.1003.CrossRefPubMed Zohlnhofer D, Ott I, Mehilli J, Schomig K, Michalk F, Ibrahim T, Meisetschlager G, von Wedel J, Bollwein H, Seyfarth M, et al: Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial. Jama. 2006, 295 (9): 1003-1010. 10.1001/jama.295.9.1003.CrossRefPubMed
28.
go back to reference Mix TC, Brenner RM, Cooper ME, de Zeeuw D, Ivanovich P, Levey AS, McGill JB, McMurray JJ, Parfrey PS, Parving HH, et al: Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease. Am Heart J. 2005, 149 (3): 408-413. 10.1016/j.ahj.2004.09.047.CrossRefPubMed Mix TC, Brenner RM, Cooper ME, de Zeeuw D, Ivanovich P, Levey AS, McGill JB, McMurray JJ, Parfrey PS, Parving HH, et al: Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease. Am Heart J. 2005, 149 (3): 408-413. 10.1016/j.ahj.2004.09.047.CrossRefPubMed
29.
go back to reference Katz O, Gil L, Lifshitz L, Prutchi-Sagiv S, Gassmann M, Mittelman M, Neumann D: Erythropoietin enhances immune responses in mice. Eur J Immunol. 2007, 37 (6): 1584-1593. 10.1002/eji.200637025.CrossRefPubMed Katz O, Gil L, Lifshitz L, Prutchi-Sagiv S, Gassmann M, Mittelman M, Neumann D: Erythropoietin enhances immune responses in mice. Eur J Immunol. 2007, 37 (6): 1584-1593. 10.1002/eji.200637025.CrossRefPubMed
30.
go back to reference Lifshitz L, Prutchi-Sagiv S, Avneon M, Gassmann M, Mittelman M, Neumann D: Non-erythroid activities of erythropoietin: Functional effects on murine dendritic cells. Mol Immunol. 2009, 46 (4): 713-721. 10.1016/j.molimm.2008.10.004.CrossRefPubMed Lifshitz L, Prutchi-Sagiv S, Avneon M, Gassmann M, Mittelman M, Neumann D: Non-erythroid activities of erythropoietin: Functional effects on murine dendritic cells. Mol Immunol. 2009, 46 (4): 713-721. 10.1016/j.molimm.2008.10.004.CrossRefPubMed
31.
go back to reference Mittelman M, Neumann D, Peled A, Kanter P, Haran-Ghera N: Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models. Proc Natl Acad Sci USA. 2001, 98 (9): 5181-5186. 10.1073/pnas.081275298.CrossRefPubMedPubMedCentral Mittelman M, Neumann D, Peled A, Kanter P, Haran-Ghera N: Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models. Proc Natl Acad Sci USA. 2001, 98 (9): 5181-5186. 10.1073/pnas.081275298.CrossRefPubMedPubMedCentral
32.
go back to reference Prutchi Sagiv S, Lifshitz L, Orkin R, Mittelman M, Neumann D: Erythropoietin effects on dendritic cells: potential mediators in its function as an immunomodulator?. Exp Hematol. 2008, 36 (12): 1682-1690. 10.1016/j.exphem.2008.07.010.CrossRefPubMed Prutchi Sagiv S, Lifshitz L, Orkin R, Mittelman M, Neumann D: Erythropoietin effects on dendritic cells: potential mediators in its function as an immunomodulator?. Exp Hematol. 2008, 36 (12): 1682-1690. 10.1016/j.exphem.2008.07.010.CrossRefPubMed
33.
go back to reference Furlani D, Klopsch C, Gabel R, Ugurlucan M, Pittermann E, Klee D, Wagner K, Li W, Wang W, Ong LL, et al: Intracardiac erythropoietin injection reveals antiinflammatory potential and improved cardiac functions detected by Forced Swim Test. Transplant Proc. 2008, 40 (4): 962-966. 10.1016/j.transproceed.2008.03.033.CrossRefPubMed Furlani D, Klopsch C, Gabel R, Ugurlucan M, Pittermann E, Klee D, Wagner K, Li W, Wang W, Ong LL, et al: Intracardiac erythropoietin injection reveals antiinflammatory potential and improved cardiac functions detected by Forced Swim Test. Transplant Proc. 2008, 40 (4): 962-966. 10.1016/j.transproceed.2008.03.033.CrossRefPubMed
34.
go back to reference Gaebel R, Klopsch C, Furlani D, Yerebakan C, Li W, Ugurlucan M, Ma N, Steinhoff G: Single high-dose intramyocardial administration of erythropoietin promotes early intracardiac proliferation, proves safety and restores cardiac performance after myocardial infarction in rats. Interact Cardiovasc Thorac Surg. 2009, 9 (1): 20-5. 10.1510/icvts.2008.191916.CrossRef Gaebel R, Klopsch C, Furlani D, Yerebakan C, Li W, Ugurlucan M, Ma N, Steinhoff G: Single high-dose intramyocardial administration of erythropoietin promotes early intracardiac proliferation, proves safety and restores cardiac performance after myocardial infarction in rats. Interact Cardiovasc Thorac Surg. 2009, 9 (1): 20-5. 10.1510/icvts.2008.191916.CrossRef
35.
go back to reference Klopsch C, Furlani D, Gabel R, Li W, Pittermann E, Ugurlucan M, Kundt G, Zingler C, Titze U, Wang W, et al: Intracardiac injection of erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model. J Cell Mol Med. 2009, 13 (4): 664-679. 10.1111/j.1582-4934.2008.00546.x.CrossRefPubMed Klopsch C, Furlani D, Gabel R, Li W, Pittermann E, Ugurlucan M, Kundt G, Zingler C, Titze U, Wang W, et al: Intracardiac injection of erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model. J Cell Mol Med. 2009, 13 (4): 664-679. 10.1111/j.1582-4934.2008.00546.x.CrossRefPubMed
Metadata
Title
Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction
Authors
Andreas Stein
Martina Knödler
Markus Makowski
Sandra Kühnel
Stefan Nekolla
Alexandra Keithahn
Eliane Weidl
Philip Groha
Maren Schürmann
Atti Saraste
Rene Botnar
Robert AJ Oostendorp
Ilka Ott
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2010
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/1471-2261-10-43

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