Oxidative stress and endothelial dysfunction

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Abstract

Oxidative stress is a hallmark of all cardiovascular risk states (e.g. hypertension, diabetes, hypercholesterolemia, cigarette smoking) and a major underlying cause of endothelial dysfunction, vascular inflammation and blood vessel pathology. Under physiological conditions, cells of the vessel wall produce reactive oxygen species (ROS) such as superoxide (O2 .-) and hydrogen peroxide (H2O2) in a deliberate and tightly regulated manner for use as second messengers in redox signalling pathways. However, in vascular pathophysiology, the production of ROS in vascular cells is elevated such that these molecules escape detoxification by cellular antioxidant pathways. When present at higher concentrations, ROS may undergo direct chemical interactions with other biomolecules. Of particular importance are the reactions between O2 .? and nitric oxide (NO), which give rise to peroxynitrite (ONOO?), and the iron-catalysed Haber-Weiss reaction between O2.? and H2O2, which gives rise to hydroxyl radicals (OH.). Peroxynitrite and OH. are extremely powerful oxidising species and, along with O2.? and H2O2, cause endothelial dysfunction through direct oxidative damage to cellular macromolecules, impairment of the NO signalling pathway, and activation of pro-inflammatory signalling cascades. Recent evidence suggests that the elevated ROS production in vascular pathophysiology is the result of a complex feed-forward mechanism whereby a primary source of ROS (NADPH oxidases) leads to dysfunction of endothelial nitric oxide synthase, xanthine oxidase and the mitochondrial electron transport chain, so that these enzymes become secondary sources of ROS and major contributors to vascular oxidative stress.
Original languageEnglish
Title of host publicationEndothelial Dysfunction and Inflammation
EditorsS M Dauphinee, A Karsan
Place of PublicationGermany
PublisherSpringer
Pages37 - 64
Number of pages28
Edition1st
ISBN (Print)978-3-0346-0167-2
Publication statusPublished - 2010

Cite this

de Dios, S. T., Sobey, C. G., & Drummond, G. R. (2010). Oxidative stress and endothelial dysfunction. In S. M. Dauphinee, & A. Karsan (Eds.), Endothelial Dysfunction and Inflammation (1st ed., pp. 37 - 64). Springer.