Smad3 Mediates Cardiac Inflammation and Fibrosis in Angiotensin II-Induced Hypertensive Cardiac Remodeling
Smad3 Mediates Cardiac Inflammation and Fibrosis in Angiotensin II-Induced Hypertensive Cardiac Remodeling
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DOI：
10.1161/hypertensionaha.109.147611
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发表时间：
2010-05-01
期刊：
影响因子：
8.3
通讯作者：
Lan, Hui Y.
中科院分区：
文献类型：
--
作者：
Huang, Xiao R.;Chung, Arthur C. K.;Lan, Hui Y.
虽然Smad 3是纤维化的关键介质，但Smad 3在高血压心血管疾病中的功能作用仍不清楚。本研究通过皮下注射血管紧张素11和原代培养Smad 3 KO心脏成纤维细胞，验证了血管紧张素II可能激活转化生长因子β/Smad 3通路介导Smad 3敲除（KO）和野生型小鼠高血压心脏重塑的假设。血管紧张素II输注后14天，Smad 3 KO和野生型小鼠均出现相同水平的高血压。然而，高血压性心脏纤维化和炎症在Smad 3野生型小鼠中发生，而在Smad 3 KO小鼠中未发生。这一点通过以下发现得到了证实：缺乏Smad 3的小鼠可以防止左心室射血分数的下降（P
Although Smad3 is a key mediator of fibrosis, the functional role of Smad3 in hypertensive cardiovascular disease remains unclear. The present study tested the hypothesis that angiotensin II may activate the transforming growth factor-beta/Smad3 pathway to mediate hypertensive cardiac remodeling in Smad3 knockout (KO) and wild-type mice by subcutaneous angiotensin 11 infusion and in the primary culture of Smad3 KO cardiac fibroblasts. Fourteen days after angiotensin II infusion, both Smad3 KO and wild-type mice developed equal levels of high blood pressure. However, hypertensive cardiac fibrosis and inflammation were developed in Smad3 wild-type but not in Smad3 KO mice. This was demonstrated by the findings that mice lacking Smad3 were protected against a fall in left ventricular ejection fraction (P