The potential beneficial effects of resveratrol on cardiovascular complications in marfan syndrome patients–insights from rodent-based animal studies

Abstract

Marfan syndrome (MFS) patients are at risk for cardiovascular disease. In particular, for aortic aneurysm formation, which ultimately can result in a life-threatening aortic dissection or rupture. Over the years, research into a sufficient pharmacological treatment option against aortopathy has expanded, mostly due to the development of rodent disease models for aneurysm formation and dissections. Unfortunately, no optimal treatment strategy has yet been identified for MFS. The biologically-potent polyphenol resveratrol (RES), that occurs in nuts, plants, and the skin of grapes, was shown to have a positive effect on aortic repair in various rodent aneurysm models. RES demonstrated to affect aortic integrity and aortic dilatation. The beneficial processes relevant for MFS included the improvement of endothelial dysfunction, extracellular matrix degradation, and smooth muscle cell death. For the wide range of beneficial effects on these mechanisms, evidence was found for the following involved pathways; alleviating oxidative stress (change in eNOS/iNOS balance and decrease in NOX4), reducing protease activity to preserve the extracellular matrix (decrease in MMP2), and improving smooth muscle cell survival affecting aortic aging (changing the miR21/miR29 balance). Besides aortic features, MFS patients may also suffer from manifestations concerning the heart, such as mitral valve prolapse and left ventricular impairment, where evidence from rodent models shows that RES may aid in promoting cardiomyocyte survival directly (SIRT1 activation) or by reducing oxidative stress (increasing superoxide dismutase) and increasing autophagy (AMPK activation). This overview discusses recent RES studies in animal models of aortic aneurysm formation and heart failure, where different advantageous effects have been reported that may collectively improve the aortic and cardiac pathology in patients with MFS. Therefore, a clinical study with RES in MFS patients seems justified, to validate RES effectiveness, and to judge its suitability as potential new treatment strategy.