Abstract

Linfang Cheng^2,†,

Qiqi Wang¹,

Dongchen Zhou¹,

Zhigang Wu²,

Ling Shen²,

Li Zhang¹ and

Jianhua Zhu¹

²State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou 31003, China

Abstract  Coronary artery disease (CAD) is a major health problem worldwide. The most severe form of CAD is acute coronary syndrome (ACS). Recent studies have demonstrated the beneficial role of atorvastatin in ACS; however, the mechanisms underlying this effect have not been fully clarified. Growing evidence indicates that activation of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays an important role in oxidative stress-induced cardiomyocyte apoptosis during ACS. In this study, we examined whether atorvastatin inhibits H2O2-induced LOX-1 expression and H9c2 cardiomyocyte apoptosis, and investigated the underlying signaling pathway. Treatment of H9c2 cardiomyocytes with H2O2 resulted in elevated expression of LOX-1 mRNA and protein, as well as increased caspase-3 and -9 protein expression and cell apoptosis. H2O2-induced LOX-1 expression, caspase protein expression, and cardiomyocyte apoptosis were attenuated by pretreatment with atorvastatin. Atorvastatin activated H2O2-inhibited phosphorylation of Akt in a concentration-dependent manner. The Akt inhibitor, LY294002, inhibited the effect of atorvastatin on inducing Akt phosphorylation and on suppressing H2O2-mediated caspase up-regulation and cell apoptosis. These findings indicate that atorvastatin protects cardiomyocyte from oxidative stress via inhibition of LOX-1 expression and apoptosis, and that activation of H2O2-inhibited phosphorylation of Akt may play an important role in the protective function of atorvastatin.

Keywords   atorvastatin; H2O2, lectin-like oxidized low-density lipoprotein receptor-1; cardiomyocyte; apoptosis; Akt

Received   2014-9-23　　

Accepted  2014-12-18

Funding  This work was supported by a grant from the Science and Technology Department of Zhejiang Province, China (No. 2010C33036).

* Correspondence address  Tel: +86-571-87236700; Fax: +86-571-87236707; E-mail: [email protected]