Nofer Jerzy-Roch
Center for Laboratory Medicine, University Hospital Münster, Albert-Schweizer-Campus 1, Geb. A1, D-48149, Münster, Germany,
Handb Exp Pharmacol. 2015;224:229-56. doi: 10.1007/978-3-319-09665-0_6.
Numerous epidemiologic studies revealed that high-density lipoprotein (HDL) is an important risk factor for coronary heart disease. There are several well-documented HDL functions such as reversed cholesterol transport, inhibition of inflammation, or inhibition of platelet activation that may account for the atheroprotective effects of this lipoprotein. Mechanistically, these functions are carried out by a direct interaction of HDL particle or its components with receptors localized on the cell surface followed by generation of intracellular signals. Several HDL-associated receptor ligands such as apolipoprotein A-I (apoA-I) or sphingosine-1-phosphate (S1P) have been identified in addition to HDL holoparticles, which interact with surface receptors such as ATP-binding cassette transporter A1 (ABCA1); S1P receptor types 1, 2, and 3 (S1P1, S1P2, and S1P3); or scavenger receptor type I (SR-BI) and activate intracellular signaling cascades encompassing kinases, phospholipases, trimeric and small G-proteins, and cytoskeletal proteins such as actin or junctional protein such as connexin43. In addition, depletion of plasma cell cholesterol mediated by ABCA1, ATP-binding cassette transporter G1 (ABCG1), or SR-BI was demonstrated to indirectly inhibit signaling over proinflammatory or proliferation-stimulating receptors such as Toll-like or growth factor receptors. The present review summarizes the current knowledge regarding the HDL-induced signal transduction and its relevance to athero- and cardioprotective effects as well as other physiological effects exerted by HDL.
众多流行病学研究表明，高密度脂蛋白（HDL）是冠心病的一个重要风险因素。HDL具有多种有充分文献记载的功能，如逆向胆固醇转运、抑制炎症或抑制血小板活化，这些功能可能解释了这种脂蛋白的抗动脉粥样硬化作用。从机制上讲，这些功能是通过HDL颗粒或其成分与位于细胞表面的受体直接相互作用，随后产生细胞内信号来实现的。除了HDL全颗粒外，还鉴定出了几种与HDL相关的受体配体，如载脂蛋白A-I（apoA-I）或鞘氨醇-1-磷酸（S1P），它们与表面受体如ATP结合盒转运体A1（ABCA1）、1型、2型和3型S1P受体（S1P1、S1P2和S1P3）或I型清道夫受体（SR-BI）相互作用，并激活包括激酶、磷脂酶、三聚体和小G蛋白以及细胞骨架蛋白（如肌动蛋白）或连接蛋白（如连接蛋白43）的细胞内信号级联反应。此外，由ABCA1、ATP结合盒转运体G1（ABCG1）或SR-BI介导的血浆细胞胆固醇耗竭被证明可间接抑制促炎或增殖刺激受体（如Toll样受体或生长因子受体）的信号传导。本综述总结了关于HDL诱导的信号转导及其与动脉粥样硬化和心脏保护作用以及HDL发挥的其他生理作用相关性的当前知识。
