Institute of Clinical Chemistry, University of Zurich and University Hospital of Zurich, 8091 Zurich, Switzerland.
Cells. 2021 Apr 28;10(5):1041. doi: 10.3390/cells10051041.
The vascular endothelium serves as a barrier between the intravascular and extravascular compartments. High-density lipoproteins (HDL) have two kinds of interactions with this barrier. First, bloodborne HDL must pass the endothelium to access extravascular tissues, for example the arterial wall or the brain, to mediate cholesterol efflux from macrophages and other cells or exert other functions. To complete reverse cholesterol transport, HDL must even pass the endothelium a second time to re-enter circulation via the lymphatics. Transendothelial HDL transport is a regulated process involving scavenger receptor SR-BI, endothelial lipase, and ATP binding cassette transporters A1 and G1. Second, HDL helps to maintain the integrity of the endothelial barrier by (i) promoting junction closure as well as (ii) repair by stimulating the proliferation and migration of endothelial cells and their progenitor cells, and by preventing (iii) loss of glycocalix, (iv) apoptosis, as well as (v) transmigration of inflammatory cells. Additional vasoprotective functions of HDL include (vi) the induction of nitric oxide (NO) production and (vii) the inhibition of reactive oxygen species (ROS) production. These vasoprotective functions are exerted by the interactions of HDL particles with SR-BI as well as specific agonists carried by HDL, notably sphingosine-1-phophate (S1P), with their specific cellular counterparts, e.g., S1P receptors. Various diseases modify the protein and lipid composition and thereby the endothelial functionality of HDL. Thorough understanding of the structure-function relationships underlying the multiple interactions of HDL with endothelial cells is expected to elucidate new targets and strategies for the treatment or prevention of various diseases.
血管内皮作为血管内和血管外隔室之间的屏障。高密度脂蛋白（HDL）与该屏障有两种相互作用。首先，血液中的 HDL 必须穿过内皮才能进入血管外组织，例如动脉壁或大脑，以介导巨噬细胞和其他细胞中的胆固醇流出，或发挥其他功能。为了完成胆固醇的逆向转运，HDL 甚至必须第二次穿过内皮，通过淋巴系统重新进入循环。跨内皮 HDL 转运是一个受调节的过程，涉及清道夫受体 SR-BI、内皮脂肪酶和 ATP 结合盒转运体 A1 和 G1。其次，HDL 通过以下方式帮助维持内皮屏障的完整性：(i) 促进连接闭合，以及 (ii) 通过刺激内皮细胞及其祖细胞的增殖和迁移来修复，以及通过防止 (iii) 糖萼丢失、(iv) 细胞凋亡以及 (v) 炎症细胞的迁移。HDL 的其他血管保护功能包括 (vi) 诱导一氧化氮 (NO) 的产生和 (vii) 抑制活性氧 (ROS) 的产生。这些血管保护功能是由 HDL 颗粒与 SR-BI 的相互作用以及 HDL 携带的特定激动剂（例如鞘氨醇-1-磷酸 (S1P)）与它们的特定细胞对应物（例如 S1P 受体）的相互作用发挥的。各种疾病会改变 HDL 的蛋白质和脂质组成，从而改变其内皮功能。深入了解 HDL 与内皮细胞的多种相互作用的结构-功能关系，有望阐明治疗或预防各种疾病的新靶点和策略。
