Trans-resveratrol down-regulates caveolin-1, up-regulates endothelial NO synthase and reduces their interaction in vascular smooth muscle and endothelial cells

Trans-resveratrol is a naturally occurring stilbene which confers cardiovascular protection. The cellular mechanism by which trans-resveratrol exerts such effects are not fully understood, although several in vivo and in vitro experiments have demonstrated that up-regulation of nitric oxide synthase (eNOS) is involved. eNOS activity is modulated by its interaction with caveolin-1 (Cav-1) in vascular endothelial and cardiac cells. This study was designed to examine the effects of trans-resveratrol on the expression and protein interactions of eNOS in vascular smooth muscle and endothelial cells. Caveolin-enriched membrane purification, Western blot, reverse-transcriptase polymerase chain reaction, and co-immunoprecipitation experiments were performed using cultured smooth muscle cells isolated from rat aorta, A7r5 cells, and HUVEC. Our results show that trans-resveratrol down-regulates Cav-1 and up-regulates eNOS in both endothelial and vascular smooth muscle cells, and that these alterations reduce the interaction of Cav-1 and eNOS in the vascular system. These effects could be beneficial in the treatment of several pathologies such as hypercholesterolemia, pulmonary hypertension, or atherosclerosis, which are characterized by decreased NO production and increased interaction of Cav-1 and eNOS.

► Several pathologies are characterized by increased interaction of Cav-1 and eNOS.
► Resveratrol is a natural polyphenol present in human diet which confers cardioprotection.
► The cellular mechanisms responsible for this protective effect are incompletely understood.
► We found that resveratrol induces de novo eNOS expression in vascular myocytes.
► Resveratrol also reduces interaction of Cav-1 and eNOS in vascular cells.