NADPH oxidase in the vasculature: Expression, regulation and signalling pathways; role in normal cardiovascular physiology and its dysregulation in hypertension

TY - JOUR

T1 - NADPH oxidase in the vasculature

T2 - Expression, regulation and signalling pathways; role in normal cardiovascular physiology and its dysregulation in hypertension

AU - Knock, Greg A.

PY - 2019/12

Y1 - 2019/12

N2 - The last 20–25 years have seen an explosion of interest in the role of NADPH oxidase (NOX) in cardiovascular function and disease. In vascular smooth muscle and endothelium, NOX generates reactive oxygen species (ROS) that act as second messengers, contributing to the control of normal vascular function. NOX activity is altered in response to a variety of stimuli, including G-protein coupled receptor agonists, growth-factors, perfusion pressure, flow and hypoxia. NOX-derived ROS are involved in smooth muscle constriction, endothelium-dependent relaxation and smooth muscle growth, proliferation and migration, thus contributing to the fine-tuning of blood flow, arterial wall thickness and vascular resistance. Through reversible oxidative modification of target proteins, ROS regulate the activity of protein tyrosine phosphatases, kinases, G proteins, ion channels, cytoskeletal proteins and transcription factors. There is now considerable, but somewhat contradictory evidence that NOX contributes to the pathogenesis of hypertension through oxidative stress. Specific NOX isoforms have been implicated in endothelial dysfunction, hyper-contractility and vascular remodelling in various animal models of hypertension, pulmonary hypertension and pulmonary arterial hypertension, but also have potential protective effects, particularly NOX4. This review explores the multiplicity of NOX function in the healthy vasculature and the evidence for and against targeting NOX for antihypertensive therapy.

AB - The last 20–25 years have seen an explosion of interest in the role of NADPH oxidase (NOX) in cardiovascular function and disease. In vascular smooth muscle and endothelium, NOX generates reactive oxygen species (ROS) that act as second messengers, contributing to the control of normal vascular function. NOX activity is altered in response to a variety of stimuli, including G-protein coupled receptor agonists, growth-factors, perfusion pressure, flow and hypoxia. NOX-derived ROS are involved in smooth muscle constriction, endothelium-dependent relaxation and smooth muscle growth, proliferation and migration, thus contributing to the fine-tuning of blood flow, arterial wall thickness and vascular resistance. Through reversible oxidative modification of target proteins, ROS regulate the activity of protein tyrosine phosphatases, kinases, G proteins, ion channels, cytoskeletal proteins and transcription factors. There is now considerable, but somewhat contradictory evidence that NOX contributes to the pathogenesis of hypertension through oxidative stress. Specific NOX isoforms have been implicated in endothelial dysfunction, hyper-contractility and vascular remodelling in various animal models of hypertension, pulmonary hypertension and pulmonary arterial hypertension, but also have potential protective effects, particularly NOX4. This review explores the multiplicity of NOX function in the healthy vasculature and the evidence for and against targeting NOX for antihypertensive therapy.

UR - http://www.scopus.com/inward/record.url?scp=85073926918&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2019.09.029

DO - 10.1016/j.freeradbiomed.2019.09.029

M3 - Review article

C2 - 31585207

AN - SCOPUS:85073926918

SN - 0891-5849

VL - 145

SP - 385

EP - 427

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -