title: Divergent roles of endothelial nitric oxide synthases system in maintaining cardiovascular homeostasis.
abstract: Accumulating evidence has demonstrated the importance of reactive oxygen species (ROS) as an essential second messenger in health and disease. Endothelial dysfunction is the hallmark of atherosclerotic cardiovascular diseases, in which pathological levels of ROS are substantially involved. The endothelium plays a crucial role in modulating tone of underlying vascular smooth muscle by synthesizing and releasing nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) factors in a distinct vessel size-dependent manner through the diverse roles of the endothelial NO synthases (NOSs) system. Endothelium-derived hydrogen peroxide (H2O2) is a physiological signaling molecule serving as one of the major EDH factors especially in microcirculations and has gained increasing attention in view of its emerging relevance for cardiovascular homeostasis. In the clinical settings, it has been reported that antioxidant supplements are unexpectedly ineffective to prevent cardiovascular events. These lines of evidence indicate the potential importance of the physiological balance between NO and H2O2/EDH through the diverse functions of endothelial NOSs system in maintaining cardiovascular homeostasis. A better understanding of cardiovascular redox signaling is certainly needed to develop novel therapeutic strategies in cardiovascular medicine. In this review, we will briefly summarize the current knowledge on the emerging regulatory roles of redox signaling pathways in cardiovascular homeostasis, with particular focus on the two endothelial NOSs-derived mediators, NO and H2O2/EDH.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Godo
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: shimo@cardio.med.tohoku.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001685:Biological Factors / Q000235:genetics / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D001685:Biological Factors; C495540:CAV1 protein, human; D051242:Caveolin 1; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Endothelial function; Endothelium-dependent hyperpolarization; Hydrogen peroxide; Nitric oxide; Nitric oxide synthase; Reactive oxygen species