A novel caffeic acid derivative prevents angiotensin II-induced cardiac remodeling.

Differentiation of cardiac fibroblasts into myofibroblasts is a critical event in the progression of cardiac fibrosis that causes pathological cardiac remodeling. Cardiac fibrosis is a hallmark of heart disease and is associated with a stiff myocardium and heart failure. This study investigated the effect of caffeic acid ethanolamide (CAEA), a novel caffeic acid derivative, on cardiac remodeling. Angiotensin (Ang) II was used to induce cardiac remodeling both in cell and animal studies. Treating cardiac fibroblast with CAEA in Ang II-exposed cell cultures reduced the expression of fibrotic marker α-smooth muscle actin (α-SMA) and collagen and the production of superoxide, indicating that CAEA inhibited the differentiation of fibroblast into myofibroblast after Ang II exposure. CAEA protects against Ang II-induced cardiac fibrosis and dysfunction in vivo, characterized by the alleviation of collagen accumulation and the recovery of ejection fraction. In addition, CAEA decreased Ang II-induced transforming growth factor-β (TGF-β) expression and reduced NOX4 expression and oxidative stress in a SMAD-dependent pathway. CAEA participated in the regulation of Ang II-induced TGF-β/SMAD/NOX4 signaling to prevent the differentiation of fibroblast into myofibroblast and thus exerted a cardioprotective effect. Our data support the administration of CAEA as a viable method for preventing the progression of Ang II-induced cardiac remodeling.