Requirement of Rac1 in the development of cardiac hypertrophy
Requirement of Rac1 in the development of cardiac hypertrophy
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DOI：
10.1073/pnas.0510444103
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发表时间：
2006-05-09
影响因子：
11.1
通讯作者：
Liao, James K.
中科院分区：
文献类型：
--
作者：
Satoh, Minoru;Ogita, Hisakazu;Liao, James K.
心肌肥大的发生部分是由NADPH氧化酶活性增加和心肌氧化应激介导的。Rho GT3，Rac，通过与gp 91（phox）和p67（phox）（其中“phox”是吞噬细胞氧化酶）的相互作用调节NADPH氧化酶活性。然而，目前尚不清楚哪种Rac亚型介导心脏中的这种作用。在这里，我们表明，Rac 1是至关重要的产生氧化应激和产生心脏肥大的成人心脏。Rac 1基因在成年小鼠心肌细胞中暂时特异性缺失（c-Rac 1（-/-））。与野生型或Rac 1杂合子小鼠相比，c-Rac 1（-/-）小鼠的心脏表现出对血管紧张素II（400 ng/kg/天，持续2周）刺激的反应，gp 91（phox）和p67（phox）相互作用、NADPH氧化酶活性和心肌氧化应激降低。这一结果与心肌肥大减少相关。这些结果表明，Rac 1是心脏肥大反应的关键，并表明靶向心肌Rac 1的治疗可能有利于心脏肥大的治疗。
The development of cardiac hypertrophy is mediated, in part, by increase in NADPH oxidase activity and myocardial oxidative stress. The Rho GTPase, Rac, regulates NADPH oxidase activity through interaction with gp91(phox) and p67(phox) (in which "phox" is phagocyte oxidase). However, it is not known which Rac isoform mediates this effect in the heart. Here we show that Rac1 is critical for generating oxidative stress and producing cardiac hypertrophy in the adult heart. The Rac1 gene was temporally and specifically deleted in adult mouse cardiomyocytes (c-Rac1(-/-)). Compared with wild-type or Rac1 heterozygous mice, the hearts of c-Rac1(-/-) mice showed decreased gp91(phox) and p67(phox) interaction, NADPH oxidase activity, and myocardial oxidative stress in response to angiotensin II (400 ng/kg per day for 2 weeks) stimulation. This result correlated with decreased myocardial hypertrophy. These results indicate that Rac1 is critical for the hypertrophic response in the heart and suggest that therapies which target myocardial Rac1 may be beneficial in the treatment of cardiac hypertrophy.