title: Oxidative stress and endothelial dysfunction: clinical evidence and therapeutic implications.
abstract: An imbalance of nitric oxide (NO) and reactive oxygen species (ROS), so-called "oxidative stress," may promote endothelial dysfunction, leading to cardiovascular complications. Activation of nicotinamide-adenine dinucleotide phosphate oxidase, xanthine oxidase, cyclooxygenase, and mitochondrial electron transport, inactivation of the antioxidant system, and uncoupling of endothelial NO synthase lead to oxidative stress along with an increase in ROS production and decrease in ROS degradation. Although experimental studies, both in vitro and in vivo, have shown a critical role of oxidative stress in endothelial dysfunction under the condition of excessive oxidative stress, there is little information on whether oxidative stress is really involved in endothelial function in humans. In a clinical setting, we showed an association between oxidative stress and endothelial function, especially in patients with renovascular hypertension as a model of increased oxidative stress and in patients with Gilbert syndrome as a model of decreased oxidative stress, through an increase in the antioxidant property of unconjugated bilirubin.
authors.affiliation: Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan. Electronic address: yhigashi@hiroshima-u.ac.jp.
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maruhashi
authors.affiliation: Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan; Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima University, Hiroshima, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005878:Gilbert Disease / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000503:physiopathology; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014527:Uric Acid / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D014527:Uric Acid; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D014969:Xanthine Oxidase; D019255:NADPH Oxidases; D001663:Bilirubin