Resveratrol (RV), a polyphenolic substance found in grape skin, is proposed to account in part for the protective effect of red wine in the cardiovascular system.
Angiotensin II (Ang II)-induced
hypertrophy of vascular smooth muscle cells (VSMCs) is a pivotal step in the development of
cardiovascular disease. The aims of this study were to test the hypothesis that RV may alter Ang II-mediated hypertrophic VSMC growth and to identify the putative underlying signaling pathways. We show that RV indeed potently inhibits Ang II-induced [(3)H]
leucine incorporation in a concentration-dependent manner (50 microM RV, 71% inhibition). Western blot analysis reveals that phosphorylation of Akt/
protein kinase B (PKB) and to a lesser extent the
mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) 1/2, both essentially involved in Ang II-mediated
hypertrophy, is dose dependently reduced by RV. Consistent with these results, we show that RV attenuates phosphorylation of the p70
ribosomal protein S6 kinase (p70(S6K)), a
kinase downstream of the ERK 1/2 as well as the Akt pathway, that is implicated in Ang II-induced
protein synthesis. Upstream of Akt/PKB RV seems to mediate its antihypertrophic effect by inhibiting phosphorylation of the
phosphatidylinositol 3-kinase (PI(3)K) rather than by activating
phosphatases. In summary, we demonstrate for the first time that RV inhibits Ang II-induced VSMC
hypertrophy, possibly by interfering mainly with the PI(3)K/Akt and p70(S6K) but also with the ERK 1/2 signaling pathway. Thus, this study delivers important new insight in the molecular pathways that may contribute to the proposed beneficial effects of RV in
cardiovascular disease.