Pivotal role of a gp91phox-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice
Pivotal role of a gp91phox-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice
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DOI：
10.1161/hc0302.103712
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发表时间：
2002-01-22
期刊：
影响因子：
37.8
通讯作者：
Shah, AM
中科院分区：
文献类型：
--
作者：
Bendall, JK;Cave, AC;Shah, AM
背景：血管紧张素II可诱导心脏和血管平滑肌（VSM）肥大。最近的研究表明，吞噬细胞型NADPH氧化酶在血管紧张素ii诱导的VSM肥大中起核心作用。NADPH氧化酶在心肌肥厚发生过程中的可能作用尚未得到研究。方法与结果：将NADPH氧化酶亚基gp91(phox) （gp91(phox-/-)）靶向破坏的小鼠（gp91(phox-/-)）和相应的野生型小鼠皮下注射亚压剂量（0.3 mg/kg/天）血管紧张素II，持续2周。血管紧张素II对两组小鼠的收缩压均无影响，但在野生型小鼠中，血管紧张素II显著增加心脏/体重比、心房利钠因子和β -肌球蛋白重链mRNA表达、心肌细胞面积和心脏胶原含量，而对gp91（phox-/-）小鼠无影响。血管紧张素II处理增加了野生型心肌NADPH氧化酶活性，但对gp91（phox-/-）没有作用。结论-含gp91（phox）的NADPH氧化酶在血管紧张素ii诱导的心肌肥厚的发生中起重要作用，不依赖于血压的变化。
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-/-).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.