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: Jonathan A Byrne, David J Grieve, Jennifer K Bendall, Jian-Mei Li, Christopher Gove, J David Lambeth, Alison C Cave, Ajay M Shah
• Journal: Circulation research (Circ Res) Vol. 93 Issue 9 Pg. 802-5 (Oct 31 2003) ISSN: 1524-4571 [Electronic] United States
• PMID: 14551238 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Isoenzymes
• Membrane Glycoproteins
• Reactive Oxygen Species
• Angiotensin II
• NADH, NADPH Oxidoreductases
• CYBB protein, human
• NADPH Oxidase 2
• NADPH Oxidase 4
• NADPH Oxidases
• Nox4 protein, mouse
• Nox-2 protein, bacteria

Topics

• Angiotensin II (pharmacology)
• Animals
• Aorta (physiopathology)
• Bacterial Proteins
• Blood Pressure
• Cardiomegaly (chemically induced, enzymology, etiology)
• Constriction, Pathologic
• Disease Models, Animal
• Disease Progression
• Hypertension (complications)
• Isoenzymes (genetics, metabolism)
• Male
• Membrane Glycoproteins (deficiency, genetics, metabolism)
• Mice
• Mice, Knockout
• Myocardium (enzymology)
• NADH, NADPH Oxidoreductases (genetics, metabolism)
• NADPH Oxidase 2
• NADPH Oxidase 4
• NADPH Oxidases (deficiency, genetics, metabolism)
• Reactive Oxygen Species (metabolism)