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Requirement of Rac1 in the development of cardiac hypertrophy
- Source :
- Proceedings of the National Academy of Sciences of the United States. May 9, 2006, Vol. 103 Issue 19, p7432, 6 p.
- Publication Year :
- 2006
-
Abstract
- 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 gp[91.sup.phox] and p[67.sup.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.sup.-/-]). Compared with wild-type or Rac1 heterozygous mice, the hearts of c-[Rac1.sup.-/-]mice showed decreased gp[91.sup.phox] and p[67.sup.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. small G protein | oxidative stress angiotensin II | NADPH oxidase
- Subjects :
- Oxidases -- Research
Oxidative stress -- Research
Science and technology
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 103
- Issue :
- 19
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.146498863