Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Rd 238, Wuhan 430060, People's Republic of China.
Hypertension. 2012 Sep;60(3):802-9. doi: 10.1161/HYPERTENSIONAHA.112.198895. Epub 2012 Jul 30.
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.
干细胞抗原 (Sca) 1 是一种糖基磷脂酰肌醇锚定蛋白，位于脂筏中，在心肌梗死和肾血管性高血压引起的心肌肥厚期间在心脏中上调。有人提出 Sca-1 在心肌梗死中起重要作用。为了研究 Sca-1 在心肌肥厚中的作用，我们在 Sca-1 心脏特异性转基因小鼠、Sca-1 敲除小鼠及其野生型同窝仔鼠中进行了主动脉缩窄术。通过超声心动图、血流动力学、病理和分子分析评估心肌肥厚。在野生型小鼠主动脉缩窄手术后，Sca-1 的表达上调并在心肌细胞中检测到。与野生型小鼠相比，Sca-1 转基因小鼠在主动脉缩窄 4 周后表现出明显减轻的心肌肥厚、纤维化和保留的心脏功能。相反，压力超负荷后 Sca-1 敲除显著加重了心肌肥厚、纤维化和功能障碍。此外，Sca-1 的过表达减弱了主动脉缩窄诱导的Src、丝裂原活化蛋白激酶和 Akt 的激活，而 Sca-1 的缺失则增强了这种激活。我们的结果表明，Sca-1 通过调节心肌细胞中的多种途径来保护心脏免受心肌肥厚和纤维化的影响。
