TY - JOUR

T1 - Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein

AU - Velagapudi, Srividya

AU - Rohrer, Lucia

AU - Poti, Francesco

AU - Feuerborn, Renate

AU - Perisa, Damir

AU - Wang, Dongdong

AU - Panteloglou, Grigorios

AU - Potapenko, Anton

AU - Yalcinkaya, Mustafa

AU - Hulsmeier, Andreas J.

AU - Hesse, Bettina

AU - Lukasz, Alexander

AU - Liu, Mingxia

AU - Parks, John S.

AU - Christoffersen, Christina

AU - Stoffel, Markus

AU - Simoni, Manuela

AU - Nofer, Jerzy-Roch

AU - von Eckardstein, Arnold

PY - 2021

Y1 - 2021

N2 - Objective: ApoM enriches S1P (sphingosine-1-phosphate) within HDL (high-density lipoproteins) and facilitates the activation of the S1P(1) (S1P receptor type 1) by S1P, thereby preserving endothelial barrier function. Many protective functions exerted by HDL in extravascular tissues raise the question of how S1P regulates transendothelial HDL transport. Approach and Results: HDL were isolated from plasma of wild-type mice, Apom knockout mice, human apoM transgenic mice or humans and radioiodinated to trace its binding, association, and transport by bovine or human aortic endothelial cells. We also compared the transport of fluorescently-labeled HDL or Evans Blue, which labels albumin, from the tail vein into the peritoneal cavity of apoE-haploinsufficient mice with (apoE-haploinsufficient mice with endothelium-specific knockin of S1P(1)) or without (control mice, ie, apoE-haploinsufficient mice without endothelium-specific knockin of S1P(1)) endothelium-specific knockin of S1P(1). The binding, association, and transport of HDL from Apom knockout mice and human apoM-depleted HDL by bovine aortic endothelial cells was significantly lower than that of HDL from wild-type mice and human apoM-containing HDL, respectively. The binding, uptake, and transport of I-125-HDL by human aortic endothelial cells was increased by an S1P(1) agonist but decreased by an S1P(1) inhibitor. Silencing of SR-BI (scavenger receptor BI) abrogated the stimulation of I-125-HDL transport by the S1P(1) agonist. Compared with control mice, that is, apoE-haploinsufficient mice without endothelium-specific knockin of S1P(1), apoE-haploinsufficient mice with endothelium-specific knockin of S1P(1) showed decreased transport of Evans Blue but increased transport of HDL from blood into the peritoneal cavity and SR-BI expression in the aortal endothelium. Conclusions: ApoM and S1P(1) 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.

AB - Objective: ApoM enriches S1P (sphingosine-1-phosphate) within HDL (high-density lipoproteins) and facilitates the activation of the S1P(1) (S1P receptor type 1) by S1P, thereby preserving endothelial barrier function. Many protective functions exerted by HDL in extravascular tissues raise the question of how S1P regulates transendothelial HDL transport. Approach and Results: HDL were isolated from plasma of wild-type mice, Apom knockout mice, human apoM transgenic mice or humans and radioiodinated to trace its binding, association, and transport by bovine or human aortic endothelial cells. We also compared the transport of fluorescently-labeled HDL or Evans Blue, which labels albumin, from the tail vein into the peritoneal cavity of apoE-haploinsufficient mice with (apoE-haploinsufficient mice with endothelium-specific knockin of S1P(1)) or without (control mice, ie, apoE-haploinsufficient mice without endothelium-specific knockin of S1P(1)) endothelium-specific knockin of S1P(1). The binding, association, and transport of HDL from Apom knockout mice and human apoM-depleted HDL by bovine aortic endothelial cells was significantly lower than that of HDL from wild-type mice and human apoM-containing HDL, respectively. The binding, uptake, and transport of I-125-HDL by human aortic endothelial cells was increased by an S1P(1) agonist but decreased by an S1P(1) inhibitor. Silencing of SR-BI (scavenger receptor BI) abrogated the stimulation of I-125-HDL transport by the S1P(1) agonist. Compared with control mice, that is, apoE-haploinsufficient mice without endothelium-specific knockin of S1P(1), apoE-haploinsufficient mice with endothelium-specific knockin of S1P(1) showed decreased transport of Evans Blue but increased transport of HDL from blood into the peritoneal cavity and SR-BI expression in the aortal endothelium. Conclusions: ApoM and S1P(1) 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.

KW - apolipoprotein

KW - endothelium

KW - lipoprotein

KW - mice

KW - sphingosine-1-phosphate

KW - SR-BI

KW - AMELIORATES ATHEROSCLEROSIS

KW - ENDOTHELIAL-CELLS

KW - HDL

KW - BINDING

KW - TRANSCYTOSIS

KW - CHOLESTEROL

KW - EFFLUX

KW - MOUSE

KW - MODEL

U2 - 10.1161/ATVBAHA.121.316725

DO - 10.1161/ATVBAHA.121.316725

M3 - Journal article

C2 - 34407633

VL - 41

SP - E468-E479

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 10

ER -