There is accumulating evidence that reactive oxygen species (ROS) play major roles in the initiation and progression of cardiovascular dysfunction associated with diseases such as hyperlipidemia, diabetes mellitus, hypertension, ischemic heart disease, and chronic heart failure. ROS produced by migrating inflammatory cells as well as vascular cells (endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts) have distinct functional effects on each cell type. These effects include cell growth, apoptosis, migration, inflammatory gene expression and matrix regulation. ROS, through regulating vascular cell function, can play a central role in normal vascular physiology, and contribute substantially to the development of cardiovascular diseases. Excessive production of ROS is an essential mechanism underlying the pathogenesis of endothelial dysfunction and cardiovascular disease. Stem cells hold great promise for tissue repair and regenerative medicine, and endothelial progenitor cells (EPC) play a significant role in neovascularization of ischemic tissue. Recent studies have shown that cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes and cigarette smoking are inversely correlated with EPC number and function. Understanding the mechanisms, that regulate EPC function may provide new insights into the pathogenesis of vasculogenesis and may promote development of specific therapies to prevent ROS production and ultimately correct EPC dysfunction. We have demonstrated the angiotensin II receptor blockers improve EPC dysfunction through antioxidative mechanisms. In the present review, we describe our current understanding of the contributions of oxidative stress to progenitor and stem cell dysfunction in cardiovascular disease and focus on the potential mechanisms that underlie oxidative stress-induced damage of progenitor and stem cells.
Cardiovascular disease, Endothelial progenitor cell, Stem cell, Reactive oxygen species, Oxidative stress
Department of Medicine,Division of Nephrology and Endocrinology, Nihon University School ofMedicine, Ooyaguchi-kami 30-1, Itabashi-ku, Tokyo 173-8610, Japan.