Genetic and Pharmacological Inhibition of Galectin-3 Prevents Cardiac Remodeling by Interfering With Myocardial Fibrogenesis

摘要: Background— Galectin-3 has been implicated in the development of organ fibrosis. It is unknown whether it a relevant therapeutic target cardiac remodeling and heart failure. Methods Results— knock-out wild-type mice were subjected to angiotensin II infusion (2.5 µg/kg for 14 days) or transverse aortic constriction 28 days provoke remodeling. The efficacy galectin-3 inhibitor N-acetyllactosamine was evaluated TGR(mREN2)27 (REN2) rats with aim reversing established after constriction. In mice, perturbations caused left-ventricular (LV) hypertrophy, decreased fractional shortening, increased LV end-diastolic pressure fibrosis ( P <0.05 versus control wild type). also developed hypertrophy but without dysfunction =NS). REN2 rats, pharmacological inhibition attenuated To elucidate beneficial effects on myocardial fibrogenesis, cultured fibroblasts treated absence presence inhibitor. Inhibition associated downregulation collagen production (collagen I III), processing, cleavage, cross-linking, deposition. Similar results observed rats. progression long-term mouse model. Conclusions— Genetic disruption attenuates fibrosis, dysfunction, subsequent failure development. Drugs binding may be potential candidates prevention reversal extensive