UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Role of NADPH Oxidase in Endothelial Ischemia/Reperfusion Injury in Humans

Loukogeorgakis, SP; van den Berg, MJ; Sofat, R; Nitsch, D; Charakida, M; Haiyee, B; de Groot, E; ... Deanfield, JE; + view all (2010) Role of NADPH Oxidase in Endothelial Ischemia/Reperfusion Injury in Humans. CIRCULATION , 121 (21) 2310 - 2316. 10.1161/CIRCULATIONAHA.108.814731.

Full text not available from this repository.

Abstract

Background-Reactive oxygen species have been implicated in the pathogenesis of ischemia/reperfusion (IR) injury. Recent studies suggest that NADPH oxidase may be a source of ROS during IR. Using an in vivo model of endothelial IR injury in the arm, we compared the response to IR in healthy volunteers with that in patients with chronic granulomatous disease. These patients have a molecular lesion in a subunit of NADPH oxidase that renders the enzyme inactive.Methods and Results-Flow-mediated dilatation was used to assess endothelial function in patients with X-linked (NOX2) or autosomal (p47) chronic granulomatous disease. IR injury was induced by 20 minutes of upper limb ischemia followed by reperfusion. Flow-mediated dilatation was determined before IR and after 20 minutes of reperfusion. The response to IR in chronic granulomatous disease patients was compared with that in age- and sex-matched healthy control subjects. Flow-mediated dilatation was expressed as mean and compared statistically with mixed linear models. IR caused a significant reduction in flow-mediated dilatation in control subjects (-5.1%; 95% confidence interval, 6.3 to 3.%; P < 0.001; n = 11). IR had no effect on endothelial function in NOX2-chronic granulomatous disease patients (-0.9; 95% confidence interval, -2.1 to 0.3; P = 0.12; n = 11). Similarly, IR-induced reduction in flow-mediated dilatation was not observed in p47-chronic granulomatous disease patients (-1.5%; 95% confidence interval, -3.1 to 0.2; P = 0.08; n = 6) in contrast to healthy control subjects (-6.5%; 95% confidence interval, -8.2 to -4.9%; P < 0.001; n = 6).Conclusions-These data indicate, for the first time in humans in vivo, that reactive oxygen species produced by NADPH oxidase are determinants of endothelial function after IR injury in humans. These findings have implications for the design of strategies to limit clinical IR injury. (Circulation. 2010; 121: 2310-2316.)

Type: Article
Title: Role of NADPH Oxidase in Endothelial Ischemia/Reperfusion Injury in Humans
DOI: 10.1161/CIRCULATIONAHA.108.814731
Keywords: granulomatous disease, chronic, endothelium, ischemia, NADPH oxidase, reactive oxygen species, reperfusion, CHRONIC GRANULOMATOUS-DISEASE, ISCHEMIA-REPERFUSION INJURY, ACUTE MYOCARDIAL-INFARCTION, INDUCED CARDIAC-HYPERTROPHY, CORONARY-ARTERY-DISEASE, NAD(P)H OXIDASE, OXIDATIVE STRESS, REACTIVE OXYGEN, ANGIOTENSIN-II, NITRIC-OXIDE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Health Informatics > Clinical Epidemiology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
URI: http://discovery.ucl.ac.uk/id/eprint/105223
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item