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

作者：Ren, Jie; Liu, Wei; Li, Guang-cai; Jin, Meng; You, Zhen-xi; Liu, Hui-guo^*; Hu, Yi^*

来源：Current Medical Science, 2018, 38(3): 405-412.

DOI：10.1007/s11596-018-1893-2

• atorvastatin
• chronic intermittent hypoxia
• myocardial remodeling
• miR-31
• protein kinase C epsilon

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 (PKC epsilon), was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes. PKC epsilon 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 (MYH7) 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 PKCe 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 PKC epsilon. These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKC epsilon and down-regulating miR-31.

• 出版日期2018-6
• 单位华中科技大学; 武汉市中心医院