TGF-β1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II

被引:398
作者
Schultz, JEJ [1 ]
Witt, SA
Glascock, BJ
Nieman, ML
Reiser, PJ
Nix, SL
Kimball, TR
Doetschman, T
机构
[1] Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA
[2] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA
[3] Univ Cincinnati, Coll Med, Dept Mol & Cellular Physiol, Cincinnati, OH 45267 USA
[4] Childrens Hosp, Med Ctr, Div Cardiol,Dept Pediat, Noninvas Cardiac Imaging & Hemodynam Res Lab, Cincinnati, OH 45229 USA
[5] Ohio State Univ, Dept Oral Biol, Columbus, OH 43210 USA
关键词
D O I
10.1172/JCI200214190
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Angiotensin II (Ang II), a potent hypertrophic stimulus, causes significant increases in TGF-beta1 gene expression. However, it is not known whether there is a causal relationship between increased levels of TGF-beta1 and cardiac hypertrophy. Echocardiographic analysis revealed that TGF-beta1-deficient mice subjected to chronic subpressor doses of Ang II had no significant change in left ventricular (LV) mass and percent fractional shortening during Ang II treatment. In contrast, Ang II-treated wild-type mice showed a >20% increase in LV mass and impaired cardiac function. Cardiomyocyte cross-sectional area was also markedly increased in Ang II-treated wild-type mice but unchanged in Ang II-treated TGF-beta1-deficient mice. No significant levels of fibrosis, mitotic growth, or cytokine infiltration were detected in Ang II-treated mice. Atrial natriuretic factor expression was similar to6-fold elevated in Ang II-treated wild-type, but not TGF-beta1-deficient mice. However, the alpha- to beta-myosin heavy chain switch did not occur in Ang II-treated mice, indicating that isoform switching is not obligatorily coupled with hypertrophy or TGF-beta1. The Ang II effect on hypertrophy was shown not to result from stimulation of the enclogenous renin-angiotensis system. These results indicate that TGF-beta1 is an important mediator of the hypertrophic growth response of the heart to Ang II.
引用
收藏
页码:787 / 796
页数:10
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