Microrna-26a protects the heart against hypertension-induced myocardial fibrosis

BACKGROUND: Hypertensive myocardial fibrosis (MF) is characterized by excessive deposition of extracellular matrix and cardiac fibroblast proliferation, which can lead to heart failure, malignant arrhythmia, and sudden death. In recent years, with the deepening of research, microRNAs have been found to have an important role in blood pressure control and maintaining normal ventricular structure and function. METHODS AND RESULTS: In this study, we first documented the downregulation of microRNA-26a (miR-26a) in the plasma and myocardium of spontaneously hypertensive rats; more importantly, miR-26a–deficient mice showed MF, whereas over-expression of miR-26a significantly prevented elevated blood pressure and inhibited MF in vivo and angiotensin II-induced fibrogenesis in cardiac fibroblasts by directly targeting connective tissue growth factor and Smad4. miR-26a inhibited cardiac fibroblast proliferation by the enhancer of zeste homolog 2/p21 pathway. CONCLUSIONS: Our study identified a novel role for miR-26a in blood pressure control and hypertensive MF and provides a possible treatment strategy for miR-26a to alleviate and reverse hypertensive MF.