Myocardial
fibrosis is an important pathological phenomenon of cardiac remodeling that is induced by
hypertension,
myocardial ischemia,
valvular heart disease,
hypertrophic cardiomyopathy, and other
heart diseases and can progress to
heart failure.
Urotensin II (UII) is regarded as a cardiovascular
autacoid/
hormone that is not only the most potent
vasoconstrictor in mammals but also involved in cardiac remodeling. However, the molecular mechanisms responsible for UII-induced cardiac
fibrosis have not yet been fully elucidated. Therefore, we aimed to investigate the effect of UII on myocardial
fibrosis in
cardiac hypertrophy and the mechanism of UII-induced cardiac
fibrosis. Cardiac tissue from mice subjected to Transverse aortic constriction (TAC) was collected.
Cardiac hypertrophy, myocardial
fibrosis, and the expression of UII
protein were assessed using echocardiography and pathological and molecular
biological analyses. The effect of UII on
fibrosis was evaluated in UII-treated mice and isolated rat primary cardiac fibroblasts, and the results indicated that UII induced significant myocardial
fibrosis and increases in the proliferation and fibrotic responses both in mice and cultured fibroblasts. Mechanistically, UII treatment induced activation of the TGF-β/Smad signaling pathway, which was suppressed by the UII receptor antagonist. In conclusion, UII plays critical roles in cardiac
fibrosis by modulating the TGF-β/Smads signaling pathway, which may be a promising therapeutic target in
hypertrophic cardiomyopathy and related problems, such as cardiac remodeling and
heart failure.