Decreased neointimal formation in Nox2-deficient mice reveals a direct role for NADPH oxidase in the response to arterial injury

被引:67
作者
Chen, ZP
Keaney, JF [1 ]
Schulz, E
Levison, B
Shan, L
Sakuma, M
Zhang, XB
Shi, C
Hazen, SL
Simon, DI
机构
[1] Harvard Univ, Sch Med, Div Cardiovasc, Brigham & Womens Hosp, Boston, MA 02115 USA
[2] Boston Univ, Sch Med, Evans Mem Dept Med, Boston, MA 02118 USA
[3] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA
[4] Cleveland Clin Fdn, Dept Cell Biol, Cleveland, OH 44195 USA
[5] Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA
关键词
D O I
10.1073/pnas.0405389101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced, in part, from NADPH oxidase in response to host invasion and tissue injury. Defects in NADPH oxidase impair host defense; however, the role of ROS and RNS in the response to tissue injury is not known. We addressed this issue by subjecting leukocyte oxidase (Nox2)-deficient (Nox2(-/-)) mice to arterial injury. Femoral artery injury was associated with increased Nox2 expression, ROS/RNS production, and oxidative protein and lipid modification in wild-type mice. In Nox2(-/-) mice, RNS-mediated protein oxidation, as monitored by protein nitrotyrosine content, was significantly diminished. This was accompanied by reduced neointimal proliferation, as monitored by intimal thickness and intimal/medial ratio, in Nox2(-/-) compared to wild-type mice. In addition, Nox2 deficiency led to reduced cellular proliferation and leukocyte accumulation. These data indicate that Nox2-mediated oxidant production has a requisite role in the response to tissue injury.
引用
收藏
页码:13014 / 13019
页数:6
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