von Eckardstein Arnold, Rohrer Lucia
Institute of Clinical Chemistry and Zurich Centre for Integrative Human Physiology, University Hospital and University of Zurich, Zurich, Switzerland.
Curr Opin Lipidol. 2009 Jun;20(3):197-205. doi: 10.1097/MOL.0b013e32832afd63.
Previously, the endothelium was considered as a passive exchange barrier of lipoproteins between plasma and extravascular tissues. This dogma is challenged by recent findings on a dual relationship between lipoproteins and endothelial permeability.
LDL and HDL as well as apolipoprotein A-I pass the intact endothelium through transcytosis by processes, which involve caveolin-1, the LDL-receptor, ATP-binding cassette transporters A1 and G1 or scavenger receptor BI. Moreover, HDL help the endothelium to maintain structural integrity and hence selective permeability for biomolecules by keeping interendothelial junctions closed, by inhibiting endothelial cell apoptosis and by stimulating endothelial proliferation, migration and tube formation as well as the recruitment and differentiation of endothelial progenitor cells in damaged parts of the endothelium. Both apolipoprotein A-I and sphingosin-1-phosphate mediate many of the protective effects of HDL on the endothelium by interacting with endothelial scavenger receptor BI and sphingosin-1-phosphate receptors, respectively, and by activating intracellular signalling cascades, including the small G protein Rac, src-kinase, phosphoinositol 3 kinase, protein kinase B (Akt) and mitogen-activated protein kinases.
The endothelium actively controls the trafficking of lipoproteins between intravascular and extravascular compartments. In addition, lipoproteins affect the integrity and permeability of the endothelium.
以往,内皮被视为血浆与血管外组织之间脂蛋白的被动交换屏障。脂蛋白与内皮通透性之间的双重关系的最新发现对这一教条提出了挑战。
低密度脂蛋白(LDL)、高密度脂蛋白(HDL)以及载脂蛋白A-I通过涉及小窝蛋白-1、LDL受体、ATP结合盒转运体A1和G1或清道夫受体BI的过程经转胞吞作用穿过完整的内皮。此外,HDL通过保持内皮细胞间连接闭合、抑制内皮细胞凋亡、刺激内皮细胞增殖、迁移和管形成以及内皮祖细胞在内皮受损部位的募集和分化,帮助内皮维持结构完整性,从而对生物分子保持选择性通透性。载脂蛋白A-I和鞘氨醇-1-磷酸分别通过与内皮清道夫受体BI和鞘氨醇-1-磷酸受体相互作用,并激活包括小G蛋白Rac、src激酶、磷酸肌醇3激酶、蛋白激酶B(Akt)和丝裂原活化蛋白激酶在内的细胞内信号级联反应,介导了HDL对内皮的许多保护作用。
内皮主动控制脂蛋白在血管内和血管外腔室之间的运输。此外,脂蛋白影响内皮的完整性和通透性。