Angiotensin II Induces the Vascular Expression of VEGF and MMP-2 in vivo: Preventive Effect of Red Wine Polyphenols

Abstract

Objective: Previous investigations have indicated that angiotensin II (Ang II)-induced hypertension and endothelial dysfunction are prevented by intake of red wine polyphenols (RWPs). Ang II has also been shown to increase the expression of VEGF and MMP-2, two major pro-inflammatory factors, in vascular diseases. Therefore, the aim of the present study was to determine whether intake of RWPs is able to prevent these effects in rats and, if so, to characterize the underlying mechanism. Methods: VEGF and endothelial NO synthase (eNOS) expression was assessed by immunofluorescence and Western blotting, MMP-2 activity by zymography, and reactive oxygen species (ROS) formation by dihydroethidine. Results: Ang II increased VEGF expression and MMP-2 activity in the aortic wall. Ang II-induced MMP-2 activation is inhibited by N^G-nitro- L-arginine and MnTMPyP. Ang II increased the expression of eNOS, the formation of ROS and the nitration of proteins. The stimulatory effects of Ang II on these factors are prevented by RWPs intake. Conclusions: Infusion of Ang II induced vascular expression of VEGF and peroxynitrite-dependent activation of MMP-2, with both effects being prevented by RWPs intake. Thus, prevention of VEGF and MMP-2 expression might be involved in the protective effect of red wine on coronary heart diseases.