Downregulation of miR-21 is involved in direct actions of ursolic acid on the heart: implications for cardiac fibrosis and hypertrophy.
PURPOSE
Myocardial fibrosis contributes to cardiac remodeling and loss of cardiac function in myocardial infarction and heart failure. This study used in vitro and in vivo models to examine the effects of ursolic acid (UA) on myocardial fibrosis and to explore its potential mechanism.


METHODS
Transverse aortic constriction (TAC) surgery was performed in mice to induce cardiac hypertrophy and fibrosis. UA was orally administered 1 week prior to TAC. Two weeks after TAC, myocardial pathology was detected using Masson's trichrome staining and transmission electron microscopy, and heart-to-body weight ratio was measured. For in vitro studies, cultured cardiac fibroblasts were treated with serum in the presence or absence of UA. The relative levels of miR-21 and p-ERK/ERK, collagen content and cell viability were measured.


RESULTS
Ursolic acid attenuated pathological cardiac hypertrophy and myocardial fibrosis in vivo induced by TAC. Downregulation of miR-21 and p-ERK/ERK were observed in myocardial fibroblasts treated with UA in a dose-dependent manner compared with the control group both in vitro and in vivo.


CONCLUSIONS
Our study demonstrates that UA can inhibit myocardial fibrosis both in vitro and in vivo, and the effects of UA on myocardial fibrosis may be due to the inhibition of miR-21/ERK signaling pathways.
['Dong|Xingli|X|', 'Liu|Shangkun|S|', 'Zhang|Lingling|L|', 'Yu|Siming|S|', 'Huo|Linman|L|', 'Qile|Muge|M|', 'Liu|Lu|L|', 'Yang|Baofeng|B|', 'Yu|Jinling|J|']
D000818:Animals D006332:Cardiomegaly D009202:Cardiomyopathies D049109:Cell Proliferation D002478:Cells, Cultured D003094:Collagen D004195:Disease Models, Animal D004305:Dose-Response Relationship, Drug D015536:Down-Regulation D048049:Extracellular Signal-Regulated MAP Kinases D005347:Fibroblasts D005355:Fibrosis D008297:Male D051379:Mice D035683:MicroRNAs D009206:Myocardium D010766:Phosphorylation D015398:Signal Transduction D014162:Transfection D014315:Triterpenes D020257:Ventricular Remodeling
miR-21 Ursolic acid Fibrosis ERK