Role of microRNA-124 in cardiomyocyte hypertrophy inducedby angiotensin II.

Abstract

Cardiac hypertrophy is a crucial predictor of heart failure and is regulated by microRNAs. MicroRNA-124 (miR-124) is regarded as a prognostic indicator for outcomes after cardiac arrest. However, whether miR-124 participates in cardiac hypertrophy remains unclear. Therefore, our study aimed to determine the role of miR-124 in angiotensin II(AngII)-induced myocardial hypertrophy and the possible mechanism. Primary cultured rat neonatal cardiomyocytes(NCMs) were transfected with miR-124 mimics or inhibitor, followed by AngII stimulation. Quantitative RT-PCR, western blot analysis and determination of cell surface area of NCMs were used to detect the hypertrophic phenotypes. We observed that miR-124 was elevated in AngII-induced hypertrophic cardiomyocytes. Cell surface area of NCMs and mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC), indicators of myocardial hypertrophy, were higher in NCMs transfected with miR-124 mimics in the presence of AngII. On the contrary, knockdown of miR-124 by its specific inhibitor could restore these courses. Furthermore, downregulation of miR-124 alleviated the increased protein level of endoplasmic reticulum (ER) stress markers 78-kDa glucose-regulated protein (Grp78) and calreticulin(CRT) in AngII-induced NCMs. In conclusion, our study shows that inhibition of miR-124 effectively suppresses AngII-induced myocardial hypertrophy, which is associated with attenuation of ER stress.

• Authors: Q Bao, L Chen, J Li, M Zhao, S Wu, W Wu, X Liu
• Journal: Cellular and molecular biology (Noisy-le-Grand, France) (Cell Mol Biol (Noisy-le-grand)) Vol. 63 Issue 4 Pg. 23-27 (Apr 29 2017) ISSN: 1165-158X [Electronic] France
• PMID: 28478799 (Publication Type: Journal Article)

Chemical References

• Calreticulin
• Endoplasmic Reticulum Chaperone BiP
• GRP78 protein, rat
• HSPA5 protein, human
• Heat-Shock Proteins
• MIRN124 microRNA, rat
• MicroRNAs
• Angiotensin II
• Natriuretic Peptide, Brain
• Atrial Natriuretic Factor
• Ventricular Myosins

Topics

• Angiotensin II (administration & dosage, metabolism)
• Animals
• Atrial Natriuretic Factor (genetics)
• Calreticulin (genetics)
• Cardiomegaly (genetics, pathology)
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (drug effects, genetics)
• Gene Expression Regulation (drug effects)
• Heat-Shock Proteins (genetics)
• Humans
• MicroRNAs (antagonists & inhibitors, genetics)
• Myocytes, Cardiac (drug effects)
• Natriuretic Peptide, Brain (genetics)
• Rats
• Ventricular Myosins (genetics)