Stem Cell Antigen 1 Protects Against Cardiac Hypertrophy and Fibrosis After Pressure Overload
Stem Cell Antigen 1 Protects Against Cardiac Hypertrophy and Fibrosis After Pressure Overload
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干细胞抗原 1 可预防压力过载后的心脏肥大和纤维化
DOI：
10.1161/hypertensionaha.112.198895
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发表时间：
2012-09-01
期刊：
影响因子：
8.3
通讯作者：
Tang, Qi-Zhu
中科院分区：
文献类型：
--
作者：
Zhou, Heng;Bian, Zhou-Yan;Tang, Qi-Zhu
干细胞抗原（Sca） 1是一种定位于脂筏的糖基磷脂酰肌醇锚定蛋白，在心肌梗死和肾血管性高血压诱导的心脏肥厚期间在心脏中上调。有研究表明，Sca-1在心肌梗死中起重要作用。为了研究Sca-1在心脏肥厚中的作用，我们对Sca-1心脏特异性转基因小鼠、Sca-1基因敲除小鼠及其野生型幼崽进行了主动脉束带实验。通过超声心动图、血流动力学、病理和分子分析评估心脏肥厚。野生型小鼠主动脉束带术后心肌细胞中Sca-1表达上调。与野生型小鼠相比，Sca-1转基因小鼠在主动脉束带4周后心肌肥厚和纤维化明显减轻，心功能得到保存。相反，Sca-1基因敲除显著加重了压力过载后的心脏肥厚、纤维化和功能障碍。此外，主动脉束带诱导的Src、丝裂原活化蛋白激酶和Akt的活化被Sca-1过表达减弱，而被Sca-1缺乏增强。我们的研究结果表明，Sca-1通过调节心肌细胞的多种途径来防止心肌肥大和纤维化。
Stem cell antigen (Sca) 1, a glycosyl phosphatidylinositol-anchored protein localized to lipid rafts, is upregulated in the heart during myocardial infarction and renovascular hypertension-induced cardiac hypertrophy. It has been suggested that Sca-1 plays an important role in myocardial infarction. To investigate the role of Sca-1 in cardiac hypertrophy, we performed aortic banding in Sca-1 cardiac-specific transgenic mice, Sca-1 knockout mice, and their wild-type littermates. Cardiac hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and molecular analyses. Sca-1 expression was upregulated and detected in cardiomyocytes after aortic banding surgery in wild-type mice. Sca-1 transgenic mice exhibited significantly attenuated cardiac hypertrophy and fibrosis and preserved cardiac function compared with wild-type mice after 4 weeks of aortic banding. Conversely, Sca-1 knockout dramatically worsened cardiac hypertrophy, fibrosis, and dysfunction after pressure overload. Furthermore, aortic banding–induced activation of Src, mitogen-activated protein kinases, and Akt was blunted by Sca-1 overexpression and enhanced by Sca-1 deficiency. Our results suggest that Sca-1 protects against cardiac hypertrophy and fibrosis via regulation of multiple pathways in cardiomyocytes.