Resveratrol exhibits inhibition effects on osteogenic differentiation of aortic valve interstitial cells by interfering with the AKT pathway

Abstract

• The expression of osteogenic markers are increased in the aortic valve tissues of patients with calcific aortic valve disease. • Resveratrol inhibits the osteogenic medium-induced osteogenic differentiation of valve interstitial cells. • Resveratrol inhibits the osteogenic differentiation of valve interstitial cells via interfering with AKT signaling pathway activation. • RES may become a potential natural drug for the treatment of calcific aortic valve disease. Resveratrol is a natural active ingredient found in many plants and has a protective effect on cardiovascular diseases. However, it has not been reported that whether resveratrol can inhibit calcific aortic valve disease(CAVD). In this study, we want to explore the effect and mechanism of resveratrol on the osteogenic differentiation of valve interstitial cells（VICs）.We first found that the expression of osteogenic markers in calcified human aortic valve. Western blotting, ALP staining and Alizarin red S staining showed that under osteogenic medium (OM) treatment, resveratrol can inhibit VICs from expressing osteogenic markers, reduce ALP content and calcium Nodule formation. Mechanistically, resveratrol can inhibit the activation of the AKT/Smad1/5/8 pathway induced by OM. We selected the AKT pathway for verification and determined that resveratrol inhibited the osteogenic differentiation of VICs by inhibiting the AKT pathway. Collectively, resveratrol may become a potential natural drug for the treatment of CAVD.