Abstract
Dysfunctional endothelium is an early change in vasculature known to be associated with atherosclerosis. Among many regulators of vascular endothelial function, p66Shc has consistently been shown to mediate endothelial dysfunction. Over more than three decades of active research in the field of the physiological function of p66Shc, regulation of vascular endothelial functions has emerged as one of the most robust effects in a broad range of pathological conditions including hyperlipidemia, diabetes, and aging. A significant understanding has been developed with respect to the molecular signaling regulating the oxidative function of p66Shc in endothelial cells and its targets and regulators. In addition, novel regulatory modifications of p66Shc controlling its oxidative function, subcellular distribution, and stability have also been reported. This review will focus on summarizing the molecular signaling regulating the oxidative function of p66Shc and its role in vascular endothelium.