Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice.
Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice.
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DOI：
10.1084/jem.20062340
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发表时间：
2007-10-01
期刊：
影响因子：
--
通讯作者：
Sessa WC
中科院分区：
文献类型：
--
作者：
Murata T;Lin MI;Huang Y;Yu J;Bauer PM;Giordano FJ;Sessa WC
小窝蛋白-1 （Cav-1）是平滑肌细胞、脂肪细胞、成纤维细胞、上皮细胞和内皮细胞（ECs）中小窝细胞器的主要结构成分。Cav-1缺失（Cav-1敲除[KO]）小鼠存活，并在血管、心肌病和肺功能障碍中显示一氧化氮（NO）的产生增加。在这项研究中，我们生成了ec特异性Cav-1重组（Cav-1 RC）小鼠，并重新检查了血管、心脏和肺表型。Cav-1 KO肺动脉平滑肌收缩力下降，内皮NO合酶激活增加，血压降低；后两种效应在Cav-1 RC小鼠中完全恢复。Cav-1 KO小鼠表现出心肌肥大、肺动脉高压和肺泡细胞增生，这是由p42/44丝裂原活化蛋白激酶和Akt的组成性激活引起的。有趣的是，在Cav-1 RC小鼠中，心肌肥大和肺动脉高压完全恢复，而肺泡增生则部分恢复，因为细支气管上皮细胞缺乏Cav-1的恢复。这些结果提供了明确的生理证据，支持细胞类型特异性Cav-1表达在血管系统、心脏和肺中控制多种表型的重要作用。
Caveolin-1 (Cav-1) is the principal structural component of caveolae organelles in smooth muscle cells, adipocytes, fibroblasts, epithelial cells, and endothelial cells (ECs). Cav-1–deficient (Cav-1 knockout [KO]) mice are viable and show increases of nitric oxide (NO) production in vasculature, cardiomyopathy, and pulmonary dysfunction. In this study, we generated EC-specific Cav-1–reconstituted (Cav-1 RC) mice and reexamined vascular, cardiac, and pulmonary phenotypes. Cav-1 KO pulmonary arteries had decreased smooth muscle contractility and increased endothelial NO synthase activation and hypotension; the latter two effects were rescued completely in Cav-1 RC mice. Cav-1 KO mice exhibited myocardial hypertrophy, pulmonary hypertension, and alveolar cell hyperproliferation caused by constitutive activation of p42/44 mitogen-activated protein kinase and Akt. Interestingly, in Cav-1 RC mice, cardiac hypertrophy and pulmonary hypertension were completely rescued, whereas alveolar hyperplasia was partially recovered because of the lack of rescue of Cav-1 in bronchiolar epithelial cells. These results provide clear physiological evidence supporting the important role of cell type–specific Cav-1 expression governing multiple phenotypes in the vasculature, heart, and lung.
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影响因子：
4.8
作者：
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通讯作者：
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作者：
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通讯作者：
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