title: Endothelial NADPH oxidases: which NOX to target in vascular disease?
abstract: NADPH oxidases (NOXs) are reactive oxygen species (ROS)-generating enzymes implicated in the pathophysiology of vascular diseases such as hypertension and stroke. Endothelial cells express four NOX isoforms including the superoxide-generating enzymes NOX1, NOX2, and NOX5 and the hydrogen peroxide-generating enzyme NOX4. Studies on arteries from patients with coronary artery disease, and in animals with experimentally induced hypertension, diabetes, or atherosclerosis, suggest that NOX1, NOX2, and NOX5 promote endothelial dysfunction, inflammation, and apoptosis in the vessel wall, whereas NOX4 is by contrast vasoprotective in increasing nitric oxide bioavailability and suppressing cell death pathways. Based on these findings and promising preclinical studies with the NOX1/NOX2 antagonist, apocynin, we suggest that the field is poised for clinical evaluation of NOX inhibitors as therapeutics for cardiovascular disease.
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia; Department of Surgery, Monash Medical Centre, Southern Clinical School, Monash University, Clayton, Victoria, Australia. Electronic address: grant.drummond@monash.edu.
authors: Grant R
authors: GR
authors: Drummond
authors: Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Clayton, Victoria, Australia; Department of Surgery, Monash Medical Centre, Southern Clinical School, Monash University, Clayton, Victoria, Australia.
authors: Christopher G
authors: CG
authors: Sobey
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014652:Vascular Diseases / Q000188:drug therapy / Q000201:enzymology*
chemical_list: D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C056558:CYBB protein, human; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C498910:NOX4 protein, human; C431571:NOX5 protein, human
keywords: NADPH oxidases; diabetes; endothelial dysfunction; hyperlipidemia; hypertension; inflammation; reactive oxygen species; selective NOX1/2 inhibitors; vascular disease