Frank Philippe G, Pavlides Stephanos, Cheung Michelle W-C, Daumer Kristin, Lisanti Michael P
Kimmel Cancer Center, Department of Cancer Biology, and Biochemistry and Molecular Biology, and Stem Cell Biology and Regenerative Medicine Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Am J Physiol Cell Physiol. 2008 Jul;295(1):C242-8. doi: 10.1152/ajpcell.00185.2008. Epub 2008 May 28.
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 caveolin-1-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.
脂蛋白代谢在多种人类疾病的发展中起着重要作用，包括冠状动脉疾病和代谢综合征。因此，深入了解调节各种脂蛋白代谢的因素是更好地理解与这些疾病发展相关变量的关键。已确定的相关因素包括小窝蛋白和小窝等调节因子。小窝是在终末分化细胞中观察到的小的质膜内陷。其最重要的蛋白质标志物小窝蛋白-1已被证明在调节多种细胞信号通路以及血浆脂蛋白代谢中起关键作用。在本文中，我们使用小窝蛋白-1缺陷（Cav-1(-/-)）小鼠研究了小窝蛋白-1在脂蛋白代谢中的作用。我们的数据表明，虽然Cav-1(-/-)小鼠的血浆甘油三酯水平升高，但它们的肝脏极低密度脂蛋白（VLDL）分泌也减少。此外，我们还发现小窝蛋白-1缺陷与高密度脂蛋白（HDL）增加有关，与从野生型小鼠获得的HDL相比，Cav-1(-/-)小鼠的这些HDL颗粒富含胆固醇酯。最后，我们的数据表明，小窝蛋白-1缺陷会阻止低密度脂蛋白（LDL）在内皮细胞中的转胞吞作用，因此，小窝蛋白-1可能参与血浆LDL水平的调节。综上所述，我们的研究表明小窝蛋白-1通过控制脂蛋白的血浆水平及其脂质组成在脂蛋白代谢调节中起重要作用。因此，小窝蛋白-1在动脉粥样硬化的发展中也可能起重要作用。
