Targeting redox signaling in the vascular wall: from basic science to clinical practice.

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.

• Authors: Charalambos Antoniades, Alexios S Antonopoulos, Jennifer K Bendall, Keith M Channon
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 15 Issue 3 Pg. 329-42 ( 2009) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 19149622 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Reactive Oxygen Species

Topics

• Animals
• Atherosclerosis (physiopathology, prevention & control)
• Clinical Trials as Topic
• Drug Delivery Systems
• Homeostasis (drug effects)
• Humans
• Muscle, Smooth, Vascular (metabolism)
• Oxidation-Reduction (drug effects)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)