Role of caveolin-1 in the regulation of lipoprotein metabolism
Role of caveolin-1 in the regulation of lipoprotein metabolism
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DOI：
10.1152/ajpcell.00185.2008
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发表时间：
2008-07-01
影响因子：
5.5
通讯作者：
Lisanti, Michael P.
中科院分区：
文献类型：
--
作者：
Frank, Philippe G.;Pavlides, Stephanos;Lisanti, Michael P.
脂蛋白代谢在包括冠状动脉疾病和代谢综合征在内的多种人类疾病的发生发展中起着重要作用。因此，对调节各种脂蛋白新陈代谢的因素的良好理解是更好地理解与这些疾病的发展相关的变量的关键。在被确定的参与者中，有监管机构，如洞穴和洞穴。小凹是在终末分化的细胞中观察到的小的质膜内陷。它们最重要的蛋白质标记物小窝蛋白-1已被证明在几个细胞信号通路的调节和血浆脂蛋白代谢的调节中发挥关键作用。在本论文中，我们研究了小凹蛋白-1在脂蛋白代谢中的作用。我们的数据显示，虽然CAV-1-/-小鼠的血浆甘油三酯水平升高，但它们也表现出肝脏极低密度脂蛋白(VLDL)分泌减少。此外，我们还发现，小窝蛋白-1缺乏与高密度脂蛋白(HDL)的增加有关，与野生型小鼠获得的高密度脂蛋白相比，CAV-1/-小鼠的这些高密度脂蛋白颗粒富含胆固醇酯。最后，我们的数据表明，小窝蛋白-1缺乏阻止了低密度脂蛋白跨内皮细胞的跨细胞传递，因此，小窝蛋白-1可能与血浆低密度脂蛋白水平的调节有关。综上所述，我们的研究表明，小窝蛋白-1通过控制他们的血浆水平和他们的脂组成，在调节脂蛋白代谢中起着重要的作用。因此，小窝蛋白-1也可能在动脉粥样硬化的发生发展中发挥重要作用。
Lipoprotein metabolism plays an important role in the development of several human diseases, including coronary artery disease and the metabolic syndrome. A good comprehension of the factors that regulate the metabolism of the various lipoproteins is therefore key to better understanding the variables associated with the development of these diseases. Among the players identified are regulators such as caveolins and caveolae. Caveolae are small plasma membrane invaginations that are observed in terminally differentiated cells. Their most important protein marker, caveolin-1, has been shown to play a key role in the regulation of several cellular signaling pathways and in the regulation of plasma lipoprotein metabolism. In the present paper, we have examined the role of caveolin-1 in lipoprotein metabolism using caveolin1-/- deficient (Cav-1-/-) mice. Our data show that, while Cav-1-/- mice show increased plasma triglyceride levels, they also display reduced hepatic very low-density lipoprotein (VLDL) secretion. Additionally, we also found that a caveolin-1 deficiency is associated with an increase in high-density lipoprotein (HDL), and these HDL particles are enriched in cholesteryl ester in Cav-1-/- mice when compared with HDL obtained from wild-type mice. Finally, our data suggest that a caveolin-1 deficiency prevents the transcytosis of LDL across endothelial cells, and therefore, that caveolin-1 may be implicated in the regulation of plasma LDL levels. Taken together, our studies suggest that caveolin-1 plays an important role in the regulation of lipoprotein metabolism by controlling their plasma levels as well as their lipid composition. Thus caveolin-1 may also play an important role in the development of atherosclerosis.