Hypoxia-induced miR-27 and miR-195 regulate ATP consumption, viability, and metabolism of rat cardiomyocytes by targeting PPARγ and FASN expression.

Abstract

This study examined whether hypoxia-induced microRNA (miRNA) upregulation was related to the inhibition of chondriosome aliphatic acid oxidation in myocardial cells under anoxia. We showed that anoxia induced high expression of hypoxia-inducible factor-1-alpha, muscle carnitine palmitoyltransferase I, and vascular endothelial growth factor in cardiomyocytes. Meanwhile, miR-27 and miR-195 were also upregulated in hypoxia-induced cardiomyocytes. Furthermore, hypoxia induction led to reductions in the adenosine triphosphate (ATP) consumption rate and oxidative metabolism as well as an increase in cardiomyocyte glycolysis. Metabolic reprogramming was reduced by hypoxia, as evidenced by the downregulation of sirtuin 1, forkhead box protein O1, sterol regulatory element-binding protein 1c, ATP citrate lyase, acetyl-coenzyme A carboxylase 2, adiponutrin, adipose triglyceride lipase, and glucose transporter type 4, while miR-27 and miR-195 inhibition partially recovered the expression of these transcription factors. In addition, hypoxia induction reduced cell viability and survival by triggering apoptosis; however, miR-27 and miR-195 inhibition partially increased cell viability. Moreover, miR-27 and miR-195 targeted the 3’untranslated regions of two key lipid-associated metabolic players, peroxisome proliferator-activated receptor gamma and fatty acid synthase. In conclusion, miR-27 and miR-195 are related to hypoxia-mediated ATP levels, glycolysis, oxidation, cell survival, and a cascade of transcription factors that control metabolism in cardiomyocytes.