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Published in: Cardiovascular Drugs and Therapy 4/2019

01-08-2019 | Myocardial Infarction | ORIGINAL ARTICLE

Resolvin D1 Attenuates Myocardial Infarction in a Rodent Model with the Participation of the HMGB1 Pathway

Authors: Rui Liu, Zhenkun Li, Qiang Wang

Published in: Cardiovascular Drugs and Therapy | Issue 4/2019

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Abstract

Purpose

Myocardial infarction (MI) is associated with high morbidity and mortality worldwide. This study aimed to explore the roles of resolvin D1 (RvD1), a metabolite of omega-3 polyunsaturated fatty acids, in protection against MI and investigate its influences on high mobility group box 1 protein (HMGB1) and related molecular mechanisms.

Methods

Three-month-old male Sprague–Dawley rats were divided into five groups: sham, MI, MI+0.02 μg RvD1, MI+0.1 μg RvD1, and MI+0.3 μg RvD1. Vehicle control or different doses of RvD1 were injected into the left ventricle (LV) cavity 5 min before MI induction. During MI induction, myocardial ischemia lasted for 45 min followed by 180 min of reperfusion. After the reperfusion, blood and LV samples were collected for biochemical examination.

Results

The MI group produced a significant increase in myocardial infarct size, serum cardiac biomarkers (LDH and CK-MB), proinflammatory cytokines (TNF-α and IL-6), and MDA levels, and a significant decrease in SOD level compared with the sham group. Moreover, a significant upregulation of gene and protein expressions of HMGB1 and its related TLR4 and NF-κB were observed in the MI group when compared with the sham group. Pretreatment of RvD1 ameliorated the biochemical changes caused by MI.

Conclusions

Our results suggested that RvD1 pretreatment exhibited protective effects against MI through downregulation of HMGB1 and its related TLR4 and NF-κB expressions.
Literature
1.
go back to reference Garg M, Khanna D, Kalra S, Balakumar P. Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction. Fundam Clin Pharmacol. 2016;30(5):394–405.CrossRefPubMed Garg M, Khanna D, Kalra S, Balakumar P. Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction. Fundam Clin Pharmacol. 2016;30(5):394–405.CrossRefPubMed
2.
go back to reference Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–e220.CrossRefPubMed Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2–e220.CrossRefPubMed
3.
go back to reference Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011;17(11):1391–401.CrossRef Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011;17(11):1391–401.CrossRef
4.
go back to reference Zhao ZQ. Postconditioning in reperfusion injury: a status report. Cardiovasc Drugs Ther. 2010;24(3):265–79.CrossRefPubMed Zhao ZQ. Postconditioning in reperfusion injury: a status report. Cardiovasc Drugs Ther. 2010;24(3):265–79.CrossRefPubMed
5.
go back to reference Ryter SW, Kim HP, Hoetzel A, Park JW, Nakahira K, Wang X, et al. Mechanisms of cell death in oxidative stress. Antioxid Redox Signal. 2007;9(1):49–89.CrossRefPubMed Ryter SW, Kim HP, Hoetzel A, Park JW, Nakahira K, Wang X, et al. Mechanisms of cell death in oxidative stress. Antioxid Redox Signal. 2007;9(1):49–89.CrossRefPubMed
6.
go back to reference Neri M, Fineschi V, Di Paolo M, Pomara C, Riezzo I, Turillazzi E, et al. Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction. Curr Vasc Pharmacol. 2015;13(1):26–36.CrossRefPubMed Neri M, Fineschi V, Di Paolo M, Pomara C, Riezzo I, Turillazzi E, et al. Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction. Curr Vasc Pharmacol. 2015;13(1):26–36.CrossRefPubMed
7.
go back to reference Du Y, Guo H, Lou H. Grape seed polyphenols protect cardiac cells from apoptosis via induction of endogenous antioxidant enzymes. J Agric Food Chem. 2007;55(5):1695–701.CrossRefPubMed Du Y, Guo H, Lou H. Grape seed polyphenols protect cardiac cells from apoptosis via induction of endogenous antioxidant enzymes. J Agric Food Chem. 2007;55(5):1695–701.CrossRefPubMed
8.
go back to reference Sun M, Dawood F, Wen WH, Chen M, Dixon I, Kirshenbaum LA, et al. Excessive tumor necrosis factor activation after infarction contributes to susceptibility of myocardial rupture and left ventricular dysfunction. Circulation. 2004;110(20):3221–8.CrossRefPubMed Sun M, Dawood F, Wen WH, Chen M, Dixon I, Kirshenbaum LA, et al. Excessive tumor necrosis factor activation after infarction contributes to susceptibility of myocardial rupture and left ventricular dysfunction. Circulation. 2004;110(20):3221–8.CrossRefPubMed
9.
go back to reference Frangogiannis NG, Lindsey ML, Michael LH, Youker KA, Bressler RB, Mendoza LH, et al. Resident cardiac mast cells degranulate and release preformed TNF-alpha, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation. 1998;98(7):699–710.CrossRefPubMed Frangogiannis NG, Lindsey ML, Michael LH, Youker KA, Bressler RB, Mendoza LH, et al. Resident cardiac mast cells degranulate and release preformed TNF-alpha, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation. 1998;98(7):699–710.CrossRefPubMed
10.
go back to reference Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58(20):2047–67.CrossRefPubMed Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58(20):2047–67.CrossRefPubMed
11.
go back to reference Nodari S, Triggiani M, Campia U, Manerba A, Milesi G, Cesana BM, et al. Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2011;57(7):870–9.CrossRefPubMed Nodari S, Triggiani M, Campia U, Manerba A, Milesi G, Cesana BM, et al. Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol. 2011;57(7):870–9.CrossRefPubMed
12.
go back to reference Serhan CN, Arita M, Hong S, Gotlinger K. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids. 2004;39(11):1125–32.CrossRefPubMed Serhan CN, Arita M, Hong S, Gotlinger K. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids. 2004;39(11):1125–32.CrossRefPubMed
13.
go back to reference Serhan CN. Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes, and neuroprotectins. Curr Opin Clin Nutr Metab Care. 2005;8(2):115–21.CrossRefPubMed Serhan CN. Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes, and neuroprotectins. Curr Opin Clin Nutr Metab Care. 2005;8(2):115–21.CrossRefPubMed
14.
15.
go back to reference Gilbert K, Bernier J, Bourque-Riel V, Malick M, Rousseau G. Resolvin D1 reduces infarct size through a phosphoinositide 3-kinase/protein kinase B mechanism. J Cardiovasc Pharmacol. 2015;66(1):72–9.CrossRefPubMed Gilbert K, Bernier J, Bourque-Riel V, Malick M, Rousseau G. Resolvin D1 reduces infarct size through a phosphoinositide 3-kinase/protein kinase B mechanism. J Cardiovasc Pharmacol. 2015;66(1):72–9.CrossRefPubMed
16.
go back to reference Lotze MT, Tracey KJ. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol. 2005;5(4):331–42.CrossRefPubMed Lotze MT, Tracey KJ. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol. 2005;5(4):331–42.CrossRefPubMed
17.
go back to reference Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;418(6894):191–5.CrossRef Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;418(6894):191–5.CrossRef
18.
go back to reference Taylor KR, Trowbridge JM, Rudisill JA, Termeer CC, Simon JC, Gallo RL. Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem. 2004;279(17):17079–84.CrossRefPubMed Taylor KR, Trowbridge JM, Rudisill JA, Termeer CC, Simon JC, Gallo RL. Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem. 2004;279(17):17079–84.CrossRefPubMed
19.
go back to reference Shimamoto A, Pohlman TH, Shomura S, Tarukawa T, Takao M, Shimpo H. Toll-like receptor 4 mediates lung ischemia-reperfusion injury. Ann Thorac Surg. 2006;82(6):2017–23.CrossRefPubMed Shimamoto A, Pohlman TH, Shomura S, Tarukawa T, Takao M, Shimpo H. Toll-like receptor 4 mediates lung ischemia-reperfusion injury. Ann Thorac Surg. 2006;82(6):2017–23.CrossRefPubMed
20.
go back to reference Kaczorowski DJ, Nakao A, Vallabhaneni R, Mollen KP, Sugimoto R, Kohmoto J, et al. Mechanisms of toll-like receptor 4 (TLR4)-mediated inflammation after cold ischemia/reperfusion in the heart. Transplantation. 2009;87(10):1455–63.CrossRefPubMedPubMedCentral Kaczorowski DJ, Nakao A, Vallabhaneni R, Mollen KP, Sugimoto R, Kohmoto J, et al. Mechanisms of toll-like receptor 4 (TLR4)-mediated inflammation after cold ischemia/reperfusion in the heart. Transplantation. 2009;87(10):1455–63.CrossRefPubMedPubMedCentral
21.
go back to reference Yan XX, Lu L, Peng WH, Wang LJ, Zhang Q, Zhang RY, et al. Increased serum HMGB1 level is associated with coronary artery disease in nondiabetic and type 2 diabetic patients. Atherosclerosis. 2009;205(2):544–8.CrossRefPubMed Yan XX, Lu L, Peng WH, Wang LJ, Zhang Q, Zhang RY, et al. Increased serum HMGB1 level is associated with coronary artery disease in nondiabetic and type 2 diabetic patients. Atherosclerosis. 2009;205(2):544–8.CrossRefPubMed
22.
go back to reference Ding HS, Yang J. High mobility group box-1 and cardiovascular diseases. Saudi Med J. 2010;31(5):486–9.PubMed Ding HS, Yang J. High mobility group box-1 and cardiovascular diseases. Saudi Med J. 2010;31(5):486–9.PubMed
23.
go back to reference Gilbert K, Bernier J, Godbout R, Rousseau G. Resolvin D1, a metabolite of omega-3 polyunsaturated fatty acid, decreases post-myocardial infarct depression. Mar Drugs. 2014;12(11):5396–407.CrossRefPubMedPubMedCentral Gilbert K, Bernier J, Godbout R, Rousseau G. Resolvin D1, a metabolite of omega-3 polyunsaturated fatty acid, decreases post-myocardial infarct depression. Mar Drugs. 2014;12(11):5396–407.CrossRefPubMedPubMedCentral
24.
go back to reference Redfors B, Shao Y, Omerovic E. Myocardial infarct size and area at risk assessment in mice. Exp Clin Cardiol. 2012;17(4):268–72.PubMedPubMedCentral Redfors B, Shao Y, Omerovic E. Myocardial infarct size and area at risk assessment in mice. Exp Clin Cardiol. 2012;17(4):268–72.PubMedPubMedCentral
25.
go back to reference Levrand S, Pesse B, Feihl F, Waeber B, Pacher P, Rolli J, et al. Peroxynitrite is a potent inhibitor of NF-{kappa}B activation triggered by inflammatory stimuli in cardiac and endothelial cell lines. J Biol Chem. 2005;280(41):34878–87.CrossRefPubMedPubMedCentral Levrand S, Pesse B, Feihl F, Waeber B, Pacher P, Rolli J, et al. Peroxynitrite is a potent inhibitor of NF-{kappa}B activation triggered by inflammatory stimuli in cardiac and endothelial cell lines. J Biol Chem. 2005;280(41):34878–87.CrossRefPubMedPubMedCentral
26.
go back to reference Di Napoli P, Taccardi AA, De Caterina R, Barsotti A. Pathophysiology of ischemia-reperfusion injury: experimental data. Ital Heart J. 2002;3(Suppl 4):24S–8S.PubMed Di Napoli P, Taccardi AA, De Caterina R, Barsotti A. Pathophysiology of ischemia-reperfusion injury: experimental data. Ital Heart J. 2002;3(Suppl 4):24S–8S.PubMed
27.
go back to reference Halade GV, Kain V, Serhan CN. Immune responsive resolvin D1 programs myocardial infarction-induced cardiorenal syndrome in heart failure. FASEB J. 2018;32(7):3717–29.CrossRefPubMedPubMedCentral Halade GV, Kain V, Serhan CN. Immune responsive resolvin D1 programs myocardial infarction-induced cardiorenal syndrome in heart failure. FASEB J. 2018;32(7):3717–29.CrossRefPubMedPubMedCentral
28.
go back to reference Weylandt KH, Chiu CY, Gomolka B, Waechter SF, Wiedenmann B. Omega-3 fatty acids and their lipid mediators: towards an understanding of resolvin and protectin formation. Prostaglandins Other Lipid Mediat. 2012;97(3–4):73–82.CrossRefPubMed Weylandt KH, Chiu CY, Gomolka B, Waechter SF, Wiedenmann B. Omega-3 fatty acids and their lipid mediators: towards an understanding of resolvin and protectin formation. Prostaglandins Other Lipid Mediat. 2012;97(3–4):73–82.CrossRefPubMed
29.
go back to reference Bento AF, Claudino RF, Dutra RC, Marcon R, Calixto JB. Omega-3 fatty acid-derived mediators 17(R)-hydroxy docosahexaenoic acid, aspirin-triggered resolvin D1 and resolvin D2 prevent experimental colitis in mice. J Immunol. 2011;187(4):1957–69.CrossRefPubMed Bento AF, Claudino RF, Dutra RC, Marcon R, Calixto JB. Omega-3 fatty acid-derived mediators 17(R)-hydroxy docosahexaenoic acid, aspirin-triggered resolvin D1 and resolvin D2 prevent experimental colitis in mice. J Immunol. 2011;187(4):1957–69.CrossRefPubMed
30.
go back to reference Jin Y, Arita M, Zhang Q, Saban DR, Chauhan SK, Chiang N, et al. Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid mediators. Invest Ophthalmol Vis Sci. 2009;50(10):4743–52.CrossRefPubMedPubMedCentral Jin Y, Arita M, Zhang Q, Saban DR, Chauhan SK, Chiang N, et al. Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid mediators. Invest Ophthalmol Vis Sci. 2009;50(10):4743–52.CrossRefPubMedPubMedCentral
31.
go back to reference Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, et al. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem. 2003;278(44):43807–17.CrossRefPubMed Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, et al. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem. 2003;278(44):43807–17.CrossRefPubMed
32.
go back to reference Halade GV, Black LM, Verma MK. Paradigm shift - metabolic transformation of docosahexaenoic and eicosapentaenoic acids to bioactives exemplify the promise of fatty acid drug discovery. Biotechnol Adv. 2018;36(4):935–53.CrossRefPubMedPubMedCentral Halade GV, Black LM, Verma MK. Paradigm shift - metabolic transformation of docosahexaenoic and eicosapentaenoic acids to bioactives exemplify the promise of fatty acid drug discovery. Biotechnol Adv. 2018;36(4):935–53.CrossRefPubMedPubMedCentral
33.
go back to reference Halade GV, Dorbane A, Ingle KA, Kain V, Schmitter JM, Rhourri-Frih B. Comprehensive targeted and non-targeted lipidomics analyses in failing and non-failing heart. Anal Bioanal Chem. 2018;410(7):1965–76.CrossRefPubMed Halade GV, Dorbane A, Ingle KA, Kain V, Schmitter JM, Rhourri-Frih B. Comprehensive targeted and non-targeted lipidomics analyses in failing and non-failing heart. Anal Bioanal Chem. 2018;410(7):1965–76.CrossRefPubMed
34.
go back to reference Kain V, Ingle KA, Colas RA, Dalli J, Prabhu SD, Serhan CN, et al. Resolvin D1 activates the inflammation resolving response at splenic and ventricular site following myocardial infarction leading to improved ventricular function. J Mol Cell Cardiol. 2015;84:24–35.CrossRefPubMedPubMedCentral Kain V, Ingle KA, Colas RA, Dalli J, Prabhu SD, Serhan CN, et al. Resolvin D1 activates the inflammation resolving response at splenic and ventricular site following myocardial infarction leading to improved ventricular function. J Mol Cell Cardiol. 2015;84:24–35.CrossRefPubMedPubMedCentral
35.
go back to reference Hu X, Ma R, Lu J, Zhang K, Xu W, Jiang H, et al. IL-23 promotes myocardial I/R injury by increasing the inflammatory responses and oxidative stress reactions. Cell Physiol Biochem. 2016;38(6):2163–72.CrossRefPubMed Hu X, Ma R, Lu J, Zhang K, Xu W, Jiang H, et al. IL-23 promotes myocardial I/R injury by increasing the inflammatory responses and oxidative stress reactions. Cell Physiol Biochem. 2016;38(6):2163–72.CrossRefPubMed
36.
go back to reference Wang SY, Cui XL, Xue FS, Duan R, Li RP, Liu GP, et al. Combined morphine and limb remote ischemic perconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury by antiapoptosis. J Surg Res. 2016;202(1):13–25.CrossRefPubMed Wang SY, Cui XL, Xue FS, Duan R, Li RP, Liu GP, et al. Combined morphine and limb remote ischemic perconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury by antiapoptosis. J Surg Res. 2016;202(1):13–25.CrossRefPubMed
37.
go back to reference Jong WM, Ten Cate H, Linnenbank AC, de Boer OJ, Reitsma PH, de Winter RJ, et al. Reduced acute myocardial ischemia-reperfusion injury in IL-6-deficient mice employing a closed-chest model. Inflamm Res. 2016;65(6):489–99.CrossRefPubMedPubMedCentral Jong WM, Ten Cate H, Linnenbank AC, de Boer OJ, Reitsma PH, de Winter RJ, et al. Reduced acute myocardial ischemia-reperfusion injury in IL-6-deficient mice employing a closed-chest model. Inflamm Res. 2016;65(6):489–99.CrossRefPubMedPubMedCentral
38.
go back to reference Kain V, Halade GV. Immune responsive resolvin D1 programs peritoneal macrophages and cardiac fibroblast phenotypes in diversified metabolic microenvironment. J Cell Physiol. 2019;234(4):3910–20.CrossRefPubMed Kain V, Halade GV. Immune responsive resolvin D1 programs peritoneal macrophages and cardiac fibroblast phenotypes in diversified metabolic microenvironment. J Cell Physiol. 2019;234(4):3910–20.CrossRefPubMed
39.
go back to reference Li J, Gong Q, Zhong S, Wang L, Guo H, Xiang Y, et al. Neutralization of the extracellular HMGB1 released by ischaemic damaged renal cells protects against renal ischaemia-reperfusion injury. Nephrol Dial Transplant. 2011;26(2):469–78.CrossRefPubMed Li J, Gong Q, Zhong S, Wang L, Guo H, Xiang Y, et al. Neutralization of the extracellular HMGB1 released by ischaemic damaged renal cells protects against renal ischaemia-reperfusion injury. Nephrol Dial Transplant. 2011;26(2):469–78.CrossRefPubMed
40.
go back to reference Zhao G, Fu C, Wang L, Zhu L, Yan Y, Xiang Y, et al. Down-regulation of nuclear HMGB1 reduces ischemia-induced HMGB1 translocation and release and protects against liver ischemia-reperfusion injury. Sci Rep. 2017;7:46272.CrossRefPubMedPubMedCentral Zhao G, Fu C, Wang L, Zhu L, Yan Y, Xiang Y, et al. Down-regulation of nuclear HMGB1 reduces ischemia-induced HMGB1 translocation and release and protects against liver ischemia-reperfusion injury. Sci Rep. 2017;7:46272.CrossRefPubMedPubMedCentral
Metadata
Title
Resolvin D1 Attenuates Myocardial Infarction in a Rodent Model with the Participation of the HMGB1 Pathway
Authors
Rui Liu
Zhenkun Li
Qiang Wang
Publication date
01-08-2019
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 4/2019
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-019-06884-y

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