Sphingosine-1-phosphate receptors 1 and 3 regulate the expression of scavenger receptor B1 in human aortic endothelial cells

Wang, Dongdong; Rohrer, Lucia; Eckardstein, Arnold von

doi:10.1101/2020.04.23.058263

Cited by 5 publications

(4 citation statements)

References 52 publications

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“…In support of interaction, it has been suggested that SR-BI tethers HDL on the cell surface and thereby increases the likelihood of S1P/S1PR interaction [ 77 , 78 ]. Moreover, our lab showed that siRNA mediated knockdowns of S1PR1 or S1PR3 reduce the expression of SR-BI [ 79 ].…”

Section: Promotion Of Endothelial Function and Integrity By Hdlmentioning

confidence: 99%

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Robert

Osto

Eckardstein

2021

Cells

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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.

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Section: Promotion Of Endothelial Function and Integrity By Hdlmentioning

confidence: 99%

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

Robert

Osto

Eckardstein

2021

Cells

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“…Moreover, we previously reported decreased SR-BI mRNA and protein expression of SR-BI in HAECs after knockdown of S1P 1 . 41…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, we previously reported decreased SR-BI mRNA and protein expression of SR-BI in HAECs after knockdown of S1P 1 . 41 The in vitro findings regarding S1P 1 activation and its role in the transendothelial transport were principally recapitulated under in vivo conditions. In mice, both treatment with the S1P 1 agonist and the endothelium-specific overexpression of S1P 1 led to increased transport of fluorescent HDL from the bloodstream into the peritoneal cavity.…”

Section: Figure 5 Effects Of S1p 1 (Sphingosine-1-phosphate Receptor ...mentioning

confidence: 94%

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

Velagapudi

Rohrer

Potì

et al. 2021

ATVB

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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 125 I-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 125 I-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.

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“…SR-BI is also regulated by S1P on both the transcriptional and the posttranslational level [189]. Interestingly, both the S1P1 receptor and the S1P3 receptor regulate the transport of HDL and LDL oppositely.…”

Section: Regulationmentioning

confidence: 99%

Transendothelial transport of lipoproteins

et al. 2020

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The accumulation of low-density lipoproteins (LDL) in the arterial wall plays a pivotal role in the initiation and pathogenesis of atherosclerosis. Conversely, the removal of cholesterol from the intima by cholesterol efflux to high density lipoproteins (HDL) and subsequent reverse cholesterol transport shall confer protection against atherosclerosis. To reach the subendothelial space, both LDL and HDL must cross the intact endothelium. Traditionally, this transit is explained by passive filtration. This dogma has been challenged by the identification of several rate-limiting factors namely scavenger receptor SR-BI, activin like kinase 1, and caveolin-1 for LDL as well as SR-BI, ATP binding cassette transporter G1, and endothelial lipase for HDL. In addition, estradiol, vascular endothelial growth factor, interleukins 6 and 17, purinergic signals, and sphingosine-1-phosphate were found to regulate transendothelial transport of either LDL or HDL. Thorough understanding of transendothelial lipoprotein transport is expected to elucidate new therapeutic targets for the treatment or prevention of atherosclerotic cardiovascular disease and the development of strategies for the local delivery of drugs or diagnostic tracers into diseased tissues including atherosclerotic lesions.

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Sphingosine-1-phosphate receptors 1 and 3 regulate the expression of scavenger receptor B1 in human aortic endothelial cells

Cited by 5 publications

References 52 publications

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions

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

Transendothelial transport of lipoproteins

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