Inhibition of Rho-kinase ameliorates myocardial remodeling and fibrosis in pressure overload and myocardial infarction: Role of TGF-β1–TAK1

► Inhibition of Rho-kinase can protect heart against TAC and MI injury. ► The beneficial effect of fasudil is associated with the profibrotic gene. ► It ameliorates myocardial remodeling, which is mediated by the TGFβ1–TAK1 pathway. Inhibition of Rho-kinase displays vasodilation property although its effect on cardiac remodeling in heart against pressure overload and ischemia has not been fully elucidated. The present study was designed to examine the effect of fasudil, a Rho-kinase (ROCK) inhibitor, on myocardial remodeling and underlying mechanisms in pressure overload and myocardial infarction (MI) mice. Pressure overload was produced by constriction of the transverse aorta (TAC) for 3 weeks. Left ventricular (LV) geometry, cardiac hypertrophy, fibrosis, and remodeling were evaluated by transthoracic echocardiography and cardiac histology. Expressions of the hypertrophic and profibrotic markers were analyzed in TAC and MI mice with or without fasudil treatment. LV cavity dilatation and dysfunction evaluated by echocardiography were significantly suppressed in the fasudil-treated MI group compared with the MI group (P