title: Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy.
abstract: Increased production of reactive oxygen species (ROS) is implicated in the development of left ventricular hypertrophy (LVH). Phagocyte-type NADPH oxidases are major cardiovascular sources of ROS, and recent data indicate a pivotal role of a gp91phox-containing NADPH oxidase in angiotensin II (Ang II)-induced LVH. We investigated the role of this oxidase in pressure-overload LVH. gp91phox-/- mice and matched controls underwent chronic Ang II infusion or aortic constriction. Ang II-induced increases in NADPH oxidase activity, atrial natriuretic factor (ANF) expression, and cardiac mass were inhibited in gp91phox-/- mice, whereas aortic constriction-induced increases in cardiac mass and ANF expression were not inhibited. However, aortic constriction increased cardiac NADPH oxidase activity in both gp91phox-/- and wild-type mice. Myocardial expression of an alternative gp91phox isoform, Nox4, was upregulated after aortic constriction in gp91phox-/- mice. The antioxidant, N-acetyl-cysteine, inhibited pressure-overload-induced LVH in both gp91phox-/- and wild-type mice. These data suggest a differential response of the cardiac Nox isoforms, gp91phox and Nox4, to Ang II versus pressure overload.
authors.affiliation: Department of Cardiology, King's College London, London, UK.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Byrne
authors.forename: David J
authors.initials: DJ
authors.lastname: Grieve
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Bendall
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Li
authors.forename: Christopher
authors.initials: C
authors.lastname: Gove
authors.forename: J David
authors.initials: JD
authors.lastname: Lambeth
authors.forename: Alison C
authors.initials: AC
authors.lastname: Cave
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001426:Bacterial Proteins; D001794:Blood Pressure; D006332:Cardiomegaly / Q000139:chemically induced / Q000201:enzymology* / Q000209:etiology*; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D018450:Disease Progression; D006973:Hypertension / Q000150:complications*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D009247:NADH, NADPH Oxidoreductases; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; C121789:Nox-2 protein, bacteria