Oxidative Stress Induces Vascular Calcification Through Modulation of the Osteogenic Transcription Factor Runx2 by AKT Signaling

摘要: Oxidative stress plays a critical role in the pathogenesis of atherosclerosis including formation lipid laden macrophages and development inflammation. However, oxidative stress-induced molecular signaling that regulates vascular calcification has not been investigated depth. Osteogenic differentiation smooth muscle cells (VSMC) is atherosclerotic lesions. An important contributor to lesions hydrogen peroxide from diverse sources cells. In this study we defined operative H2O2-induced VSMC calcification. We found H2O2 promotes phenotypic switch contractile osteogenic phenotype. This response was associated with an increased expression transactivity Runx2, key transcription factor for differentiation. The essential Runx2 further confirmed by depletion overexpression. Inhibition using short hairpin RNA blocked calcification, adenovirus-mediated overexpression alone induced H2O2-activated AKT induction concurrently. blockage did cause apoptosis. Taken together, our data demonstrate AKT-mediated