Original Article Stiftung DHD原始文章基金会.pdfVIP

Original Article Endothelial Nitric Oxide Synthase Uncoupling Impairs Endothelial Progenitor Cell Mobilization and Function in Diabetes Thomas Thum,1 Daniela Fraccarollo,1 Maximilian Schultheiss,1 Sabrina Froese,1 Paolo Galuppo,1 Julian D. Widder,1,2 Dimitrios Tsikas,3 Georg Ertl,1 and Johann Bauersachs1 Uncoupling of the endothelial nitric oxide synthase (eNOS) resulting in superoxide anion (O2) formation instead of nitric oxide (NO) causes diabetic endothelial dysfunction. ardiovascular disease is a common complica- eNOS regulates mobilization and function of endothelial tion of diabetes (1,2). Endothelial dysfunction progenitor cells (EPCs), key regulators of vascular repair. as a first step in the pathogenesis of diabetes We postulate a role of eNOS uncoupling for reduced num- C promotes arteriosclerosis (3). Mechanistically, ber and function of EPC in diabetes. EPC levels in diabetic uncoupling of the endothelial nitric oxide synthase (eNOS) patients were significantly reduced compared with those of in blood vessels of diabetic patients leads to excessive control subjects. EPCs from diabetic patients produced superoxide anion (O2 ) production and diminishes nitric excessive O2 and showed impaired migratory capacity oxide (NO) availability (4–6). The underlying molecular compared with nondiabetic control subjects. NOS inhibi- G events are not completely clear, but reduction of the tion with N -nitro-L-arginine attenuated O2 production essential eNO