Targeting Redox Signaling in the Vascular Wall: From Basic Science to Clinical Practice

Authors: Antoniades, Charalambos; Antonopoulos, Alexios S.; Bendall, Jennifer K.; Channon, Keith M.

Source: Current Pharmaceutical Design, Volume 15, Number 3, January 2009 , pp. 329-342(14)

Publisher: Bentham Science Publishers

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Abstract:

Oxidative stress is a key feature in vascular homeostasis. Reactive oxygen species (ROS) are produced by multiple enzymatic sources located in various anatomical structures of the vascular wall, such as the vascular endothelium, the smooth muscle cells and inflammatory cells infiltrating sub-endothelial space and the rest of the vascular wall. Although ROS behave as signaling molecules regulating important aspects of vascular physiology, their excess generation is harmful. Further to the cytotoxic effect of ROS in the vascular wall, they also activate various redox sensitive transcription pathways, regulating the expression of proinflammatory molecules with strong pro-atherogenic effects. The activation of redox-sensitive enzymatic systems in the vascular wall such as matrix metalloproteinases as well as the impairment of endothelial function have a significant impact on vascular elasticity and vascular mechanics in general. The impairment of vascular mechanics has a significant impact on vascular homeostasis, promoting atherogenesis. It is therefore crucial to regulate vascular redox signaling, by developing therapeutic strategies able to target the effectively intracellular ROS bioavailability. Statins, angiotensin converting enzyme inhibitors, thiazolidinediones, folates, tetrahydrobiopterin and other therapeutic strategies seem promising in targeting vascular redox signaling, although it is still unclear which of these treatments have the potential to effectively prevent atherogenesis. Future studies need to define the key redox sensitive pathways in the vascular wall in order to develop effective therapeutic strategies against atherosclerosis.

Keywords: Redox signaling; free radicals; antioxidants; vascular mechanics; endothelial nitric oxide synthase; NADPH oxidase; tetrahydrobiopterin; atherosclerosis

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161209787354230

Affiliations: 1: Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.

Publication date: 2009-01-01

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Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

Targeting Redox Signaling in the Vascular Wall: From Basic Science to Clinical Practice

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