title: Atorvastatin protects cardiomyocytes from oxidative stress by inhibiting LOX-1 expression and cardiomyocyte apoptosis.
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.
authors: Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 31003, China lzhang2000@yahoo.com.
authors: Lei
authors: L
authors: Zhang
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou 31003, China.
authors: Linfang
authors: L
authors: Cheng
authors: Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 31003, China.
authors: Qiqi
authors: Q
authors: Wang
authors: Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 31003, China.
authors: Dongchen
authors: D
authors: Zhou
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou 31003, China.
authors: Zhigang
authors: Z
authors: Wu
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou 31003, China.
authors: Ling
authors: L
authors: Shen
authors: Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 31003, China.
authors: Li
authors: L
authors: Zhang
authors: Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 31003, China.
authors: Jianhua
authors: J
authors: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002867:Chromones; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009025:Morpholines; C495136:OLR1 protein, rat; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000069059:Atorvastatin; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9
keywords: Akt; H2O2, lectin-like oxidized low-density lipoprotein receptor-1; apoptosis; atorvastatin; cardiomyocyte