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

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

Authors :
Ren, Jie
Liu, Wei
Li, Guang-cai
Jin, Meng
You, Zhen-xi
Liu, Hui-guo
Hu, Yi
Source :
Current Medical Science; June 2018, Vol. 38 Issue: 3 p405-412, 8p
Publication Year :
2018

Abstract

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 (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 PKCε. These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.

Details

Language :
English
ISSN :
20965230 and 2523899X
Volume :
38
Issue :
3
Database :
Supplemental Index
Journal :
Current Medical Science
Publication Type :
Periodical
Accession number :
ejs45889369
Full Text :
https://doi.org/10.1007/s11596-018-1893-2