NOX1, 2, 4, 5: counting out oxidative stress

Abstract

For decades, oxidative stress has been discussed as a key mechanism of endothelial dysfunction and cardiovascular disease. However, attempts to validate and exploit this hypothesis clinically by supplementing antioxidants have failed. Nevertheless, this does not disprove the oxidative stress hypothesis. As a certain degree of reactive oxygen species (ROS) formation appears to be physiological and beneficial. To reduce oxidative stress therapeutically, two alternative approaches are being developed. One is the repair of key signalling components that are compromised by oxidative stress. These include uncoupled endothelial nitric oxide (NO) synthase and oxidized/heme-free NO receptor soluble guanylate cyclase. A second approach is to identify and effectively inhibit the relevant source(s) of ROS in a given disease condition. A highly likely target in this context is the family of NADPH oxidases. Animal models, including NOX knockout mice and new pharmacological inhibitors of NADPH oxidases have opened up a new era of oxidative stress research and have paved the way for new cardiovascular therapies.LINKED ARTICLESThis article is part of a themed issue on Vascular Endothelium in Health and Disease. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-3

Lipid Peroxidation and Antioxidants in Arterial Hypertension

“…However, there is limited evidence supporting the use of antioxidants to lower blood pressure in human hypertensive patients [5,92]. Nevertheless, the failure of these studies does not exclude a role for oxidative stress in human essential hypertension but instead suggests that the antioxidant supplementation approach was not the appropriate therapeutic strategy [96].…”

“…Although there is considerable evidence of oxidative stress involvement in the pathophysiology of hypertension, the attempts to demonstrate benefits from antioxidant therapy in human cardiovascular diseases have been very disappointing [5,96,283]. Most of the large trials regarding the effects of diet supplementation with Vitamin C, Vitamin E and -carotene failed to show significant improvements in blood pressure and other cardiovascular endpoints [5,283].…”

“…radicals [108]. Uric acid is a highly abundant aqueous antioxidant, considered to be the main contributor for the antioxidant capacity in the plasma [96,132]. It has the ability to quenche HO .…”

“…Traditional approaches to evaluate oxidant status have frequently relied on indirect measurements of ROS bioavailability (e.g. evaluation of prooxidant and antioxidant activity, oxidized products from ROS and the GSH/GSSG ratio) as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to therapeutic intervention [9,[96][97][98][99].…”

Reactive oxygen species delay control of lymphocytic choriomeningitis virus

“…24 Oxidative stress plays a critical role in liver, cardiovascular, Alzheimer's and autoimmune diseases. [25][26][27][28] Neutrophil infiltrates can be observed during autoimmunity such as rheumatoid arthritis, 29 and a recent report shows that neutrophil p47phox phosphorylation is elevated in patients with rheumatoid arthritis. 30 Surprisingly, p47phox-deficient mice have shown higher incidences of autoimmunity such as rheumatoid arthritis.…”