Downregulation of MicroRNA-19b contributes to angiotensin II-induced overexpression of connective tissue growth factor in cardiomyocytes

Abstract

Objectives: The present study was designed to decipher the molecular mechanisms underlying angiotensin (Ang) II-induced overexpression of connective tissue growth factor (CTGF) in cultured cardiomyocytes. Methods: Cardiomyocytes isolated from 1- to 3-day-old neonatal rats were cultured and treated with 100 nM Ang II with or without pretreatment with 10 nM telmisartan, an Ang II type 1 receptor antagonist. The role of microRNA (miR)-19b in the regulation of Ang II-induced CTGF expression was evaluated in cultured cardiomyocytes with quantitative real-time reverse transcription polymerase chain reaction and Western blot analysis. Results: We provide several lines of evidence to show that miR-19b contributes to the Ang II-induced overexpression of CTGF in cultured cardiomyocytes. Firstly, administration of Ang II decreased the level of miR-19b dramatically (p < 0.05 vs. control), which was abolished by telmisartan. Secondly, Ang II increased the level of CTGF significantly (p < 0.05 vs. control), which was also prevented by pretreatment with telmisartan. Thirdly, overexpression of miR-19b decreased CTGF levels (p < 0.05 vs. control). Finally, transfection of miR-19b into cardiomyocytes prevented the upregulation of CTGF induced by Ang II. Conclusion: Downregulation of miR-19b contributes to Ang II-induced overexpression of CTGF in cultured cardiomyocytes. © 2013 S. Karger AG, Basel.