Endothelial primary cilia inhibit atherosclerosis
Endothelial primary cilia inhibit atherosclerosis
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DOI：
10.15252/embr.201541019
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发表时间：
2016-02-01
期刊：
影响因子：
7.7
通讯作者：
Reiter, Jeremy F.
中科院分区：
文献类型：
--
作者：
Dinsmore, Colin;Reiter, Jeremy F.
初级纤毛是大多数哺乳动物细胞上存在的基于微管的结构，对于细胞间信号传导非常重要。纤毛存在于内皮细胞的一个子集中，它们投射到血管腔中，并被认为是血流的机械传感器。为了测试内皮纤毛的体内作用，我们有条件地删除了小鼠内皮细胞中纤毛发生所需的基因 Ift88。我们发现内皮初级纤毛对于哺乳动物血管发育是可有可无的。纤毛在小鼠主动脉中分布不均匀，但在血管分支点和高曲率部位丰富。这些相同的部位容易形成动脉粥样硬化斑块，促使我们研究纤毛是否参与动脉粥样硬化。在喂食高脂肪、高胆固醇饮食的 Apoe(-/-) 小鼠中，去除内皮纤毛会增加动脉粥样硬化，这表明纤毛可以预防动脉粥样硬化。去除内皮纤毛会增加炎症基因表达并降低 eNOS 活性，表明内皮纤毛抑制主动脉中促动脉粥样硬化信号传导。
Primary cilia are microtubule-based structures present on most mammalian cells that are important for intercellular signaling. Cilia are present on a subset of endothelial cells where they project into the vessel lumen and are implicated as mechanical sensors of blood flow. To test the in vivo role of endothelial cilia, we conditionally deleted Ift88, a gene required for ciliogenesis, in endothelial cells of mice. We found that endothelial primary cilia were dispensable for mammalian vascular development. Cilia were not uniformly distributed in the mouse aorta, but were enriched at vascular branch points and sites of high curvature. These same sites are predisposed to the development of atherosclerotic plaques, prompting us to investigate whether cilia participate in atherosclerosis. Removing endothelial cilia increased atherosclerosis in Apoe(-/-) mice fed a high-fat, high-cholesterol diet, indicating that cilia protect against atherosclerosis. Removing endothelial cilia increased inflammatory gene expression and decreased eNOS activity, indicating that endothelial cilia inhibit pro-atherosclerotic signaling in the aorta.