Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein.
Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein.
复制标题
DOI：
10.1161/atvbaha.121.316725
复制
发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
von Eckardstein A
中科院分区：
文献类型：
--
作者：
Velagapudi S;Rohrer L;Poti F;Feuerborn R;Perisa D;Wang D;Panteloglou G;Potapenko A;Yalcinkaya M;Hülsmeier AJ;Hesse B;Lukasz A;Liu M;Parks JS;Christoffersen C;Stoffel M;Simoni M;Nofer JR;von Eckardstein A
载脂蛋白M（ApoM）富集高密度脂蛋白（HDL）内的鞘氨醇-1-磷酸（S1 P），并促进S1 P激活S1 P1受体，从而保护内皮屏障功能。HDL在血管外组织中发挥的许多保护功能提出了一个问题，即S1 P如何调节HDL的跨内皮转运。从野生型小鼠、Apom敲除小鼠、人apoM转基因小鼠或人的血浆中分离HDL，并进行放射性碘标记以追踪其通过牛或人主动脉内皮细胞（分别为BAEC和HAEC）的结合、缔合和转运。我们还比较了荧光标记的HDL或伊文思蓝（标记白蛋白）从尾静脉转运到apoE-单倍型不足小鼠的腹膜腔中的情况，其中有（S1 P1-iECKI）或没有（CTRL）内皮特异性敲入S1 P1。BAECs对Apom基因敲除小鼠HDL和人apoM缺失HDL的结合、结合和转运分别显著低于野生型小鼠HDL和人apoM缺失HDL。HAECs对125 I-HDL的结合、摄取和转运可被S1 P1激动剂增加，但被S1 P1抑制剂降低。清道夫受体BI（SR-BI）的沉默消除了S1 P1激动剂对125 I-HDL转运的刺激。与CTRL相比，S1 P1-iECKI显示伊文氏蓝的转运减少，但HDL从血液转运到腹膜腔和腹膜内皮中的SR-BI表达增加。ApoM和S1 P1促进HDL跨内皮转运。它们对白蛋白和HDL的跨内皮转运的相反作用表明HDL通过特定机制而不是被动过滤通过内皮屏障。
Apolipoprotein M (ApoM) enriches sphingosine-1-phosphate (S1P) within high density lipoproteins (HDL) and facilitates the activation of the S1P1 receptor by S1P, thereby preserving endothelial barrier function. Many protective functions exerted by HDL in extravascular tissues raise the question how S1P regulates transendothelial HDL transport. HDL were isolated from plasma of wild type mice, Apom knock-out mice, human apoM transgenic mice or humans and radioiodinated to trace its binding, association, and transport by bovine or human aortic endothelial cells (BAECs and HAECs, respectively). We also compared the transport of fluorescently-labeled HDL or Evan’s Blue, which labels albumin, from the tail vein into the peritoneal cavity of apoE-haploinsufficient mice with (S1P1-iECKI) or without (CTRL) endothelium specific knock-in of S1P1. The binding, association, and transport of HDL from Apom knock-out mice and human apoM-depleted HDL by BAECs was significantly lower than that of HDL from wild type mice and human apoM containing HDL, respectively. The binding, uptake, and transport of 125I-HDL by HAECs was increased by an S1P1 agonist but decreased by an S1P1 inhibitor. Silencing of scavenger receptor BI (SR-BI) abrogated the stimulation of 125I-HDL transport by the S1P1 agonist. Compared to CTRL, S1P1-iECKI showed decreased transport of Evan’s Blue but increased transport of HDL from blood into the peritoneal cavity and SR-BI expression in the aortal endothelium. ApoM and S1P1 promote transendothelial HDL transport. Their opposite effect on transendothelial transport of albumin and HDL indicates that HDL passes endothelial barriers by specific mechanisms rather than passive filtration.