Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice.
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.
Bendall
Jennifer K
JK
Department of Cardiology, Guy's, King's and St Thomas' School of Medicine, King's College London, London, UK.
Cave
Alison C
AC
Heymes
Christophe
C
Gall
Nicholas
N
Shah
Ajay M
AM
D000804:Angiotensin II; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D001794:Blood Pressure; D006332:Cardiomegaly / Q000139:chemically induced / Q000201:enzymology* / Q000209:etiology*; D003094:Collagen / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000502:physiology*; D009929:Organ Size; D012333:RNA, Messenger / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D013481:Superoxides; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D003094:Collagen; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D018995:Myosin Heavy Chains