NADPH Oxidase 1 Plays a Key Role in Diabetes Mellitus-Accelerated Atherosclerosis
Stephen P Gray, Elyse Di Marco, Jun Okabe, Cedric Szyndralewiez, Freddy Heitz, Augusto C Montezano, Judy B de Haan, Christine Koulis, Assam El-Osta, Karen L Andrews, Jaye PF Chin-Dusting, Rhian M Touyz, Kirstin Wingler, Mark E Cooper, Harald HHW Schmidt, Karin A Jandeleit-Dahm
Circulation | LIPPINCOTT WILLIAMS & WILKINS | Published : 2013
BACKGROUND: In diabetes mellitus, vascular complications such as atherosclerosis are a major cause of death. The key underlying pathomechanisms are unclear. However, hyperglycemic oxidative stress derived from NADPH oxidase (Nox), the only known dedicated enzyme to generate reactive oxygen species appears to play a role. Here we identify the Nox1 isoform as playing a key and pharmacologically targetable role in the accelerated development of diabetic atherosclerosis. METHODS AND RESULTS: Human aortic endothelial cells exposed to hyperglycemic conditions showed increased expression of Nox1, oxidative stress, and proinflammatory markers in a Nox1-siRNA reversible manner. Similarly, the specifi..View full abstract
Awarded by National Health & Medical Research Council project grant of Australia
Awarded by Juvenile Diabetes Research Foundation
This work was supported by the National Health & Medical Research Council (NHMRC 1005851) project grant of Australia, the Juvenile Diabetes Research Foundation (JDRF-4-2010-528), the National Heart Foundation of Australia, the Diabetes Australia Research Trust, and the FP7 framework program. Dr Jandeleit-Dahm is supported by a NHMRC Senior Research Fellowship, and Dr Cooper is an Australian Fellow for the NHMRC and a JDRF Scholar. Dr Schmidt is supported by the EU (Marie Curie International Reintegration Grant and ERC Advanced Grant). Dr Touyz was supported through a Canada Research Chair/Canadian Institutes of Health Research (CIHR)/Canadian Foundation for Innovation award. Dr Montezano was supported through a fellowship from the CIHR.C.S. and F. H. are paid employees and own shares in Genkyotex SA, Geneva, Switzerland. The other authors report no conflicts.