Novel isoforms of NADPH-oxidase in cerebral vascular control

Pharmacology & Therapeutics
Alyson A MillerChristopher G Sobey

Abstract

Reactive oxygen species (ROS) are thought to play an important role in the initiation and progression of a variety of vascular diseases. Furthermore, accumulating evidence indicates that ROS may also serve as important cell signalling molecules for the regulation of normal vascular function. Recently, a novel family of proteins (Nox1, 2 and 4) that act as the catalytic subunit of the superoxide (O2-) producing enzyme NADPH-oxidase has been discovered in vascular cells. There is now preliminary evidence suggesting that NADPH-oxidase-derived ROS may serve as a physiological vasodilator mechanism in the cerebral circulation. Moreover, the activity of NADPH-oxidase is profoundly greater in cerebral versus systemic arteries. Studies have shown that Nox1, Nox2 (also known as gp91phox) and Nox4 are all expressed in cerebral arteries, suggesting that multiple isoforms of NADPH-oxidase may be important for ROS production by cerebral arteries. Enhanced NADPH-oxidase activity is associated with several vascular-related diseases, including hypertension, stroke, subarachnoid haemorrhage and Alzheimer's dementia; however, the consequences of this for cerebral vascular function are controversial. For example, there is some evidence suggesting...Continue Reading

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