The Communication Between Sphingosine-1-Phosphate Receptors And Scavenger Receptor Class B Type 1 In Endothelial Cells

Background/Objectives: Prevention of macrophage apoptosis in advanced atherosclerotic lesions can help stop atherosclerosis progression to vulnerable plaques. High density lipoprotein (HDL) can protect macrophages from apoptosis that has been induced by a variety of agents. We hypothesize that this is the consequence of the sphingolipid, sphingosine-1-phosphate (S1P), specifically carried by HDL, and transferred to S1P receptor 1 (S1PR1) on the cells via the HDL receptor, scavenger receptor class B type 1 (SR-B1). Methods: Apoptosis was induced in murine peritoneal macrophages from wild type and different knockout mice with the ER stress inducing agent tunicamycin. Apoptosis was then observed and detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling through fluorescent microscopy. All experiments were conducted with an n of 3 or 4. Results: Treatment of cells with HDL protected them against tunicamycin induced apoptosis. In contrast, pre-treatment of HDL with S1P lyase, which irreversibly cleaves S1P, eliminated the ability of HDL to protect macrophages. Furthermore, HDL-dependent protection of macrophages against apoptosis required both the HDL receptor SRB1 and the S1PR1. Inhibitor of SRB1’s lipid transport activity also prevented HDL dependant protection against apoptosis. Conclusions: These results suggest that the HDL mediated protection of macrophages against apoptosis may involve SRB1 mediated delivery of S1P from HDL to the S1PR1. Understanding the mechanisms by which HDL elicits atheroprotective signalling in macrophages will provide insight into new targets for therapeutic intervention.

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High Density Lipoprotein Mediated Protection of Macrophages against Apoptosis Requires Scavenger Receptor Class B Type 1 Activity and Sphingosine-1-Phosphate

Atherosclerosis Supplements ◽

10.1016/j.atherosclerosissup.2018.04.097 ◽

2018 ◽

Vol 32 ◽

pp. 34

Author(s):

Kevin Chathely ◽

Leticia González ◽

Bernardo L. Trigatti

Keyword(s):

High Density Lipoprotein ◽

Scavenger Receptor ◽

Density Lipoprotein ◽

High Density ◽

Scavenger Receptor Class ◽

Class B ◽

Sphingosine 1 Phosphate

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Silencing of the scavenger receptor (Class B – Type 1) gene using siRNA-loaded chitosan nanaoparticles in a HepG2 cell model

Colloids and Surfaces B Biointerfaces ◽

10.1016/j.colsurfb.2014.10.045 ◽

2014 ◽

Vol 123 ◽

pp. 930-937 ◽

Cited By ~ 26

Author(s):

Mariane M. Farid ◽

Rania M. Hathout ◽

Mahmoud Fawzy ◽

Khaled Abou-Aisha

Keyword(s):

Hepg2 Cell ◽

Cell Model ◽

Scavenger Receptor ◽

Scavenger Receptor Class ◽

Class B

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Linoleic acid treatment increases the expression of scavenger receptor class B type 1 (SR-B1) in in-vitro model

Atherosclerosis ◽

10.1016/j.atherosclerosis.2021.06.382 ◽

2021 ◽

Vol 331 ◽

pp. e128

Author(s):

N.-A. Azemi ◽

L. Abu-Bakar ◽

N. Ismail ◽

V. Sevakumaran ◽

T.-S. Tengku-Muhammad

Keyword(s):

Linoleic Acid ◽

Acid Treatment ◽

In Vitro Model ◽

Scavenger Receptor ◽

Scavenger Receptor Class ◽

Class B ◽

Vitro Model

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Abstract 624: Endothelial Scavenger Receptor Class B, Type I (SR-BI) Mediates LDL Uptake by the Artery Wall and Promotes Atherosclerosis in Hypercholesterolemic Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.624 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Linzhang Huang ◽

Ken Chambliss ◽

Mohamed Ahmed ◽

Chieko Mineo ◽

Philip W Shaul

Keyword(s):

Endothelial Cells ◽

Scavenger Receptor ◽

Plasma Lipid ◽

Density Lipoprotein ◽

Type I ◽

Artery Wall ◽

Blocking Antibody ◽

Scavenger Receptor Class ◽

Class B ◽

Ldl Uptake

In endothelial cells, high density lipoprotein cholesterol (HDL) binding to scavenger receptor class B, type I (SR-BI) promotes the production of the antiatherogenic signaling molecule nitric oxide (NO) and also endothelial repair. To study how SR-BI in endothelium impacts atherosclerosis, we bred newly-created floxed SR-BI mice, vascular endothelial cadherin promoter-driven Cre recombinase transgenic (VECad-Cre), and apoE -/- mice to generate apoE -/- with normal endothelial SR-BI expression (SR-BI ECIN ;apoE -/- ) or selective deletion of SR-BI from endothelium (SR-BI ECOUT ;apoE -/- ). At weaning all mice were placed on an atherogenic diet (20% fat, 1.25% cholesterol), and plasma lipid profiles and atherosclerosis were evaluated 8 weeks later. Endothelial deletion of SR-BI did not alter the plasma lipid profile. Surprisingly, male SR-BI ECOUT ;apoE -/- mice displayed 63% less atherosclerosis in the en face aorta than male SR-BI ECIN ;apoE -/- mice, aortic root lesions were comparably affected, and similar findings were obtained in females. Recognizing that SR-BI binds both HDL and low density lipoprotein cholesterol (LDL), to then discern how endothelial SR-BI promotes atherosclerosis we determined using Di-I-labeled oxidized LDL (oxLDL) if SR-BI influences oxLDL uptake by endothelial cells. Such uptake is the first step in the endothelial transcytosis that delivers LDL to the artery wall to initiate atherogenesis. OxLDL uptake by primary human aortic endothelial cells was blunted by 87% by SR-BI blocking antibody, and it was also decreased by SR-BI deletion via siRNA, and by the chemical inhibitor of SR-BI BLT-1. Furthermore, SR-BI blocking antibody and BLT-1 caused marked declines in endothelial oxLDL transcytosis. Moreover, 4 hours following IV administration, oxLDL uptake in aorta was decreased by 84% in SR-BI ECOUT ;apoE -/- versus SR-BI ECIN ;apoE -/- mice. These collective findings indicate that endothelial SR-BI plays an important role in atherogenesis, and that it likely does so by mediating LDL uptake into the artery wall. They further suggest that there are mechanisms that govern LDL transport across endothelium that may be targeted to provide novel means to combat atherosclerosis.

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