title: Effect of carvedilol on cardiomyocyte apoptosis in a rat model of myocardial infarction: a role for toll-like receptor 4.
abstract: OBJECTIVE
  Toll-like receptor 4 (TLR4) is crucial in cardiomyocyte apoptosis induced by myocardial infarction (MI) and carvedilol has been reported to have anti-apoptotic effects. We hypothesized that the effects of this agent are in part mediated through TLR4 signaling pathways.
  
  
  METHODS
  A total of 48 rats were randomized to the following groups before surgery: sham-operated group (n = 8), MI group (n = 10) and three carvedilol-treatment groups (n = 30, 2 mg/kg, 10 mg/kg and 30 mg/kg). Sham and MI groups were given vehicle and carvedilol groups received different dose carvedilol, by direct gastric gavage for 7 days. On the 4(th) day of drug or vehicle administration, MI model was produced by ligating the left anterior descending coronary artery. On day 3 after MI, apoptosis was assessed by TdT-UTP nick-end assay; the levels of expression of Bax, Bcl-2, TLR4 and nuclear factor-κB (NF-κB) in infarcted myocardium were analyzed by immunohistochemistry.
  
  
  RESULTS
  Carvedilol ameliorated MI-induced apoptosis in a dose-dependent manner. In parallel, carvedilol also decreased the ratio of Bax to Bcl-2, the expression of TLR4 and NF-κB induced by MI. The extent of apoptosis and Bax-Bcl-2 ratio was strongly correlated with the TLR4 levels.
  
  
  CONCLUSIONS
  This study suggests that the short-term administration of carvedilol can significantly alleviate cardiomyocyte apoptosis in the infarcted myocardium probably by inhibiting the excessive expression of TLR4 and NF-κB induced by infarction.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Liu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Changhao
authors.initials: C
authors.lastname: Wu
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011412:Propanolamines / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D019253:Proto-Oncogene Proteins c-bcl-2; D051197:Toll-Like Receptor 4; D051028:bcl-2-Associated X Protein; D000077261:Carvedilol
keywords: Apoptosis; carvedilol; myocardial infarction; toll-like receptor 4