Pivotal Role of a gp91 phox -Containing NADPH Oxidase in Angiotensin II-Induced Cardiac Hypertrophy in Mice

作者：Jennifer K. Bendall, Alison Cave, Christophe Heymes, Nicholas Gall, Ajay M. Shah · 发表于：Circulation · 年份：2002 · DOI：10.1161/hc0302.103712 · 被引用次数：527 · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Cardiac Fibrosis and Remodeling、Redox biology and oxidative stress

BACKGROUND: Angiotensin II induces both cardiac and vascular smooth muscle (VSM) hypertrophy. Recent studies suggest a central role for a phagocyte-type NADPH oxidase in angiotensin II-induced VSM hypertrophy. The possible involvement of an NADPH oxidase in the development of cardiac hypertrophy has not been studied. Methods and Results- Mice with targeted disruption of the NADPH oxidase subunit gp91(phox) (gp91(phox-/-)) and matched wild-type mice were subjected to subcutaneous angiotensin II infusion at a subpressor dose (0.3 mg/kg/day) for 2 weeks. Systolic blood pressure was unaltered by angiotensin II in either group. Angiotensin II significantly increased heart/body weight ratio, atrial natriuretic factor and beta-myosin heavy chain mRNA expression, myocyte area, and cardiac collagen content in wild-type but not gp91(phox-/-) mice. Angiotensin II treatment increased myocardial NADPH oxidase activity in wild-type but not gp91(phox-/-) mice. CONCLUSIONS: A gp91(phox)-containing NADPH oxidase plays an important role in the development of angiotensin II-induced cardiac hypertrophy, independent of changes in blood pressure.