Abstract
 
Vol 47 No. 3: 174-182 [PDF] [Full Text]
 
Atorvastatin protects cardiomyocytes from oxidative stress by inhibiting LOX-1 expression and cardiomyocyte apoptosis
 
Lei Zhang1,†,*, Linfang Cheng2,†, Qiqi Wang1, Dongchen Zhou1, Zhigang Wu2, Ling Shen2, Li Zhang1 and Jianhua Zhu1

1Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 31003, China
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]

 
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