TGF-β1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II
TGF-β1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II
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DOI：
10.1172/jci200214190
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发表时间：
2002-03-01
影响因子：
15.9
通讯作者：
Doetschman, T
中科院分区：
文献类型：
--
作者：
Schultz, JEJ;Witt, SA;Doetschman, T
血管紧张素II（Ang II）是一种强有力的肥大刺激物，可导致TGF-β 1基因表达显著增加。然而，目前尚不清楚TGF-β 1水平升高与心脏肥大之间是否存在因果关系。超声心动图分析显示，TGF-β 1缺陷小鼠慢性降压剂量的血管紧张素II没有显着变化，左心室（LV）的质量和百分比缩短血管紧张素II治疗期间。相比之下，Ang II治疗的野生型小鼠显示LV质量增加>20%，心脏功能受损。在Ang II治疗的野生型小鼠中，心肌细胞横截面积也显著增加，但在Ang II治疗的TGF-β 1缺陷小鼠中无变化。在Ang II处理的小鼠中没有检测到显著水平的纤维化、有丝分裂生长或细胞因子浸润。在Ang II处理的野生型小鼠中，心房利钠因子的表达升高了6倍，而TGF-β 1缺陷小鼠则没有。然而，α-到β-肌球蛋白重链开关没有发生在血管紧张素II治疗的小鼠，表明亚型转换不是强制性的肥大或TGF-β 1。血管紧张素II对肥大的作用不是由于刺激血管生成性肾素-血管紧张素系统。这些结果表明，TGF-β 1是心脏对Ang II的肥大性生长反应的重要介质。
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.