The miR-19a/b family positively regulates cardiomyocyte hypertrophy by targeting atrogin-1 and MuRF-1

摘要: Progressive cardiac hypertrophy owing to pathological stimuli, such as pressure overload, is frequently associated with the development of heart failure, a major cause morbidity and mortality worldwide. Growing evidence has shown that miRNAs are extensively involved in pathogenesis hypertrophy. In present study, we examined hypothesis miR-19a/b family acts key regulator apoptosis. Forced overexpression was sufficient induce rat neonatal cardiomyocytes. Luciferase assays revealed directly target anti-hypertrophic genes atrogin-1 MuRF-1 (muscle RING-finger protein-1). The endogenous expressions were down-regulated by . Pro-hypertrophic calcineurin/NFAT (nuclear factor activated T-cells) signalling elevated markedly presence miR-19b , calcineurin inhibitor CsA (cyclosporin A) PKC (protein kinase C) GF10923X significantly attenuated -mediated increase cell size expression hypertrophic markers. Furthermore, led increased survival through up-regulation NFAT gene encoding α-crystallin-B repression pro-apoptotic Bim (Bcl-2-interacting mediator death) under ER (endoplasmic reticulum) stress conditions. Taken together, results study demonstrate regulates phenotypes cardiomyocytes via suppression multiple direct genes.