AVE 3085, a novel endothelial nitric oxide synthase enhancer, attenuates cardiac remodeling in mice through the Smad signaling pathway

Abstract

AVE 3085 is a novel endothelial nitric oxide synthase enhancer. Although AVE 3085 treatment has been shown to be effective in spontaneously restoring endothelial function in hypertensive rats, little is known about the effects and mechanisms of AVE 3085 with respect to cardiac remodeling. The present study was designed to examine the effects of AVE 3085 on cardiac remodeling and the mechanisms underlying the effects of this compound. Mice were subjected to aortic banding to induce cardiac remodeling and were then administered AVE 3085 (10mgkgday−1, orally) for 4weeks. At the end of the treatment, the aortic banding-treated mice exhibited significant elevations in cardiac remodeling, characterized by an increase in left ventricular weight relative to body weight, an increase in the area of collagen deposition, an increase in the mean myocyte diameter, and increases in the gene expressions of the hypertrophic markers atrial natriuretic peptide (ANP) and β-MHC. These indexes were significantly decreased in the AVE 3085-treated mice. Furthermore, AVE 3085 treatment reduced the expression and activation of the Smad signaling pathway in the aortic banding-treated mice. Our data showed that AVE 3085 attenuated cardiac remodeling, and this effect was possibly mediated through the inhibition of Smad signaling.