Effect of carvedilol on cardiomyocyte apoptosis in a rat model of myocardial infarction: A role for toll-like receptor 4
Qingwei Liu1, Jianhua Zhang1, Yan Xu1, Ying Huang1, Changhao Wu2
1 Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
2 Faculty of Health and Medical Sciences, Division of Biochemistry and Physiology, University of Surrey, Guildford, GU2 7XH, United Kingdom
Objectives: 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.
Materials and 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.
Conclusion: 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.
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022
|How to cite this article:|
Liu Q, Zhang J, Xu Y, Huang Y, Wu C. Effect of carvedilol on cardiomyocyte apoptosis in a rat model of myocardial infarction: A role for toll-like receptor 4.Indian J Pharmacol 2013;45:458-463
|How to cite this URL:|
Liu Q, Zhang J, Xu Y, Huang Y, Wu C. Effect of carvedilol on cardiomyocyte apoptosis in a rat model of myocardial infarction: A role for toll-like receptor 4. Indian J Pharmacol [serial online] 2013 [cited 2021 Apr 19 ];45:458-463
Available from: https://www.ijp-online.com/article.asp?issn=0253-7613;year=2013;volume=45;issue=5;spage=458;epage=463;aulast=Liu;type=0