Atorvastatin Attenuates Myocardial Hypertrophy Induced by Chronic Intermittent Hypoxia In Vitro Partly through miR-31/PKCε Pathway  

作　　者：Jie REN Wei LIU Guang-cai LI Meng JIN Zhen-xi YOU Hui-guo LIU Yi HU 

机构地区：[1]Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2]Department of Respiratory and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430010, China

出　　处：《Current Medical Science》2018年第3期405-412,共8页当代医学科学（英文）

基　　金：This project was supported by the National Natural Science Foundation of China （No. 81370185 and No. 81570080）.

摘　　要：Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia （CIH）. However, little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy, and whether specific hypertrophyrelated microRNAs are involved in the modulation. MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia. This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy. H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days. The size of cardiomyocytes, and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR, respectively. MiR-31 mimic or Ro 31-8220, a specific inhibitor of protein kinase C epsilon （PKCε）, was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes. PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting. The results showed that CIH induced obvious enlargement of cardiomyocytes, which was paralleled with increased atrial natriuretic peptide （ANP）, brain natriuretic peptide （BNP）, and slow/beta cardiac myosin heavy-chain （MYHT） mRNA levels. All these changes were reversed by the treatment with atorvastatin. Meanwhile, miR-31 was increased by CIH in vitro. Of note, the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31. Moreover, overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes. Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε. These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia （CIH）. However, little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy, and whether specific hypertrophyrelated microRNAs are involved in the modulation. MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia. This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy. H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days. The size of cardiomyocytes, and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR, respectively. MiR-31 mimic or Ro 31-8220, a specific inhibitor of protein kinase C epsilon （PKCε）, was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes. PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting. The results showed that CIH induced obvious enlargement of cardiomyocytes, which was paralleled with increased atrial natriuretic peptide （ANP）, brain natriuretic peptide （BNP）, and slow/beta cardiac myosin heavy-chain （MYHT） mRNA levels. All these changes were reversed by the treatment with atorvastatin. Meanwhile, miR-31 was increased by CIH in vitro. Of note, the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31. Moreover, overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes. Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε. These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.

关 键 词：ATORVASTATIN chronic intermittent hypoxia myocardial remodeling miR-31 protein kinase C epsilon 

分 类 号：R542.2[医药卫生—心血管疾病]