title: Cardioprotective effect of carvedilol: inhibition of apoptosis in H9c2 cardiomyocytes via the TLR4/NF-κB pathway following ischemia/reperfusion injury.
abstract: Carvedilol is a non-selective β-blocker used in the treatment of cardiovascular disease, including myocardial ischemia. The aim of the present study was to investigate the molecular mechanisms underlying the effects of carvedilol on simulated ischemia/reperfusion (SI/R)-induced cardiomyocyte apoptosisin vitro. H9c2 cardiomyocytes were incubated with either a vehicle or an ischemic buffer during hypoxia followed by reoxygenation with or without carvedilol. In two additional groups, toll-like receptor 4 (TLR4) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) were inhibited by a TLR4 antibody and pyrrolidine dithiocarbamate, respectively. The results revealed that carvedilol markedly decreased SI/R-induced apoptosis in a concentration-dependent manner, as demonstrated by flow-cytometric analysis. This effect was shown to be associated with an increase in the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X (Bax) protein ratio and concurrent reductions in the expression levels of TLR4 and NF-κB. These results suggest that carvedilol provides significant cardioprotection against SI/R-induced injury in H9c2 cardiomyocytes, an effect likely to be mediated through the TLR4/NF-κB signaling pathway.
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cardiovascular Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ji
keywords: H9c2; apoptosis; carvedilol; ischemia/reperfusion; toll-like receptor 4/nuclear factor κ-light-chain-enhancer of activated B cells