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Resveratrol attenuated homocysteine-induced apoptosis of rat ventricular myocytes

2014; Elsevier BV; Volume: 177; Issue: 1 Linguagem: Inglês

10.1016/j.ijcard.2014.09.033

1874-1754

Yu Liu, Qiaojing Liu, Zhina Hu, Qiujia Shen, Hongyan Liang, Xiaofeng Jiang,

Esophageal and GI Pathology

Elevated homocysteine level in the plasma is a new independent important risk factor of ischemic heart diseases, stroke, dementia, Alzheimer's disease, renal failure, osteoporotic fracture, etc. In particular, increasing evidence has revealed a strong association of hyperhyomocystemia with cardiovascular diseases including heart failure, atrial fibrillation and venous thromboembolism, so that serum homocysteine level has been considered as a diagnostic marker of myocardial infraction and an important predictor of mortality for patients with coronary artery diseases (CAD) [ [1] Nygard O. Nordrehaug J.E. Refsum H. Ueland P.M. Farstad M. Vollset S.E. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997; 337: 230-236 Crossref PubMed Scopus (1645) Google Scholar ]. Hyperhomocysteinemia may be caused by many lifestyle and pathological factors such as genetic defect, smoking and coffee consumption [ 2 Tsai M.Y. Welge B.G. Hanson N.Q. Bignell M.K. Vessey J. Schwichtenberg K. et al. Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases. Atherosclerosis. 1999; 143: 163-170 Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar , 3 Nygard O. Refsum H. Ueland P.M. Stensvold I. Nordrehaug J.E. Kvale G. et al. Coffee consumption and plasma total homocysteine: the Hordaland homocysteine study. Am J Clin Nutr. 1997; 65: 136-143 PubMed Google Scholar ]. The patients with the T133C mutation in the cystathionine-beta-synthase (CBS) gene and the thermolabile C677T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene have increased homocysteine level and higher predisposition to premature coronary artery diseases [ [2] Tsai M.Y. Welge B.G. Hanson N.Q. Bignell M.K. Vessey J. Schwichtenberg K. et al. Genetic causes of mild hyperhomocysteinemia in patients with premature occlusive coronary artery diseases. Atherosclerosis. 1999; 143: 163-170 Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar ]. The heavy coffee consumption and cigarette smoking were correlated with high homocysteine in the plasma as well [ [3] Nygard O. Refsum H. Ueland P.M. Stensvold I. Nordrehaug J.E. Kvale G. et al. Coffee consumption and plasma total homocysteine: the Hordaland homocysteine study. Am J Clin Nutr. 1997; 65: 136-143 PubMed Google Scholar ]. Although arguing remains about homocysteine acting as causes or results of cardiovascular diseases, more and more studies provided the evidence to support that increased serum homocysteine level contributes to the damages on myocardial and vascular tissues [ 4 Suhara T. Fukuo K. Yasuda O. Tsubakimoto M. Takemura Y. Kawamoto H. et al. Homocysteine enhances endothelial apoptosis via upregulation of Fas-mediated pathways. Hypertension. 2004; 43: 1208-1213 Crossref PubMed Scopus (82) Google Scholar , 5 Rasmussen L.M. Hansen P.R. Ledet T. Homocysteine and the production of collagens, proliferation and apoptosis in human arterial smooth muscle cells. APMIS. 2004; 112: 598-604 Crossref PubMed Scopus (17) Google Scholar ]. The transgenic mice with high concentration of plasma homocysteine demonstrated severely impaired cardiac relaxation and contractile function, with increased cardiomyocyte death after ischemia reperfusion [ [6] Wang X. Cui L. Joseph J. Jiang B. Pimental D. Handy D.E. et al. Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress. J Mol Cell Cardiol. 2012; 52: 753-760 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar ]. In vitro study also reported that increased homocysteine level impaired cardiomyocyte contractility and promoted apoptosis by enhancing reactive oxygen species (ROS), TRX and p38 MAPK pathways [ [6] Wang X. Cui L. Joseph J. Jiang B. Pimental D. Handy D.E. et al. Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress. J Mol Cell Cardiol. 2012; 52: 753-760 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar ]. Its underlying mechanisms were related to the disturbance of intracellular calcium homeostasis and cellular apoptosis [ 4 Suhara T. Fukuo K. Yasuda O. Tsubakimoto M. Takemura Y. Kawamoto H. et al. Homocysteine enhances endothelial apoptosis via upregulation of Fas-mediated pathways. Hypertension. 2004; 43: 1208-1213 Crossref PubMed Scopus (82) Google Scholar , 6 Wang X. Cui L. Joseph J. Jiang B. Pimental D. Handy D.E. et al. Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress. J Mol Cell Cardiol. 2012; 52: 753-760 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar , 7 Moshal K.S. Tipparaju S.M. Vacek T.P. Kumar M. Singh M. Frank I.E. et al. Mitochondrial matrix metalloproteinase activation decreases myocyte contractility in hyperhomocysteinemia. Am J Physiol Heart Circ Physiol. 2008; 295: H890-H897 Crossref PubMed Scopus (84) Google Scholar ]. Therefore, it will be an important therapeutic strategy to treat homocysteine-related cardiovascular diseases by inhibiting homocysteine-induced apoptosis of cardiomyocyte and vascular myocytes.