Atorvastatin Attenuates Myocardial Hypertrophy Induced by Chronic Intermittent Hypoxia In Vitro Partly through miR-31/PKCε Pathway / 华中科技大学学报(医学)(英德文版)
Journal of Huazhong University of Science and Technology (Medical Sciences)
; (6): 405-412, 2018.
Article
in Zh
| WPRIM
| ID: wpr-737217
Responsible library:
WPRO
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 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.
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Language:
Zh
Journal:
Journal of Huazhong University of Science and Technology (Medical Sciences)
Year:
2018
Type:
Article