title: Resveratrol improves myocardial ischemia and ischemic heart failure in mice by antagonizing the detrimental effects of fractalkine*.
abstract: OBJECTIVE
  To test the hypothesis that resveratrol would improve cardiac remodeling by inhibiting the detrimental effects of fractalkine. We previously reported that fractalkine exacerbates heart failure. Furthermore, this study sought to determine whether resveratrol targets fractalkine to improve myocardial ischemia and cardiac remodeling.
  
  
  METHODS
  Randomized and controlled laboratory investigation.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Neonatal rat cardiac cells and C57BL/6 mice.
  
  
  METHODS
  Cardiac cells were treated with recombinant mouse soluble fractalkine for 24 hrs or pretreated with 25 µM resveratrol. Cardiomyocytes were exposed to anoxia/reoxygenation, H2O2, or pretreatment with resveratrol. Ex vivo murine hearts were perfusioned with soluble fractalkine or pretreated with resveratrol after global ischemia. Mice were subjected to the left coronary artery ligation to induce myocardial infarction and randomized to treatment with resveratrol or vehicle alone for 42 days.
  
  
  RESULTS
  In a murine myocardial infarction model, we found that resveratrol increased survival and delayed the progression of cardiac remodeling evaluated by serial echocardiography. At 6 wks, the heart weight/body weight ratio, lung weight/body weight ratio, and old infarct size were significantly smaller in resveratrol-treated mice than in untreated myocardial infarction mice. In cultures of neonatal rat cells, exposure to soluble fractalkine increased the atrial natriuretic peptide expression by cardiomyocytes, matrix metalloproteinase-9 and procollagen expression by fibroblasts, and intercellular adhesion molecule-1 expression by microvascular endothelial cells, while it decreased autophagy in cardiomyocytes. All these effects were blocked by coculture with resveratrol. The methyl thiazolyl tetrazolium assay showed that soluble fractalkine reduced the viability of cultured cardiomyocytes during exposure to anoxia/reoxygenation or H2O2, while pretreatment with resveratrol blocked this effect. Perfusion of ex vivo murine hearts with soluble fractalkine after global ischemia led to an increase of infarct size, which was prevented by pretreatment with resveratrol.
  
  
  CONCLUSIONS
  Resveratrol alleviates the deleterious effects of fractalkine on myocardial ischemia and thus reduces subsequent cardiac remodeling.
authors.affiliation: Department of Cardiology, and Organ Failure Key Laboratory of Ministry of Education, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Wanling
authors.initials: W
authors.lastname: Xuan
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.forename: Ci
authors.initials: C
authors.lastname: Chen
authors.forename: Baihe
authors.initials: B
authors.lastname: Chen
authors.forename: Wenqing
authors.initials: W
authors.lastname: Zhang
authors.forename: Dingli
authors.initials: D
authors.lastname: Xu
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D054428:Chemokine CX3CL1 / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004562:Electrocardiography; D006333:Heart Failure / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D054428:Chemokine CX3CL1; D010975:Platelet Aggregation Inhibitors; D013267:Stilbenes; D000077185:Resveratrol