Novel approaches to treat oxidative stress and cardiovascular diseases.
Reduction-oxidation (redox) reactions that generate reactive oxygen species (ROS) such as hydrogen peroxide and superoxide have been identified as important chemical processes that regulate signal transduction. The findings of increased ROS in association with endothelial dysfunction has given rise to the "antioxidant hypothesis": since ROS are increased in hypertension, atherosclerosis and vascular injury, then inhibiting oxidative stress with antioxidants should decrease cardiovascular events. Preliminary efforts with antioxidant vitamins like beta-carotene, vitamin C and vitamin E have shown no clinical benefits. Here we discuss a specific "redox signaling hypothesis." We propose that physiologic stimuli such as steady laminar flow regulate the redox state of cells and tissues thereby modulating signaling molecules that are redox sensitive. Here we show that steady laminar flow inhibits tumor necrosis factor (TNF) signaling and inflammation in endothelial cells. We have identified a specific redox molecule-thioredoxin interacting protein (TXNIP)-as a key redox regulator of inflammation in blood vessels. We suggest that modifying the redox state of the vasculature is an attractive therapeutic approach if we target specific redox dependent pathways such as TXNIP.
Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. bradford_berk@urmc.rochester.edu
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D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000628:therapy*; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008955:Models, Cardiovascular; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013879:Thioredoxins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002352:Carrier Proteins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C445672:Txnip protein, mouse; D013879:Thioredoxins