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

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 t...

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Autores principales: Robert, Jérôme, Osto, Elena, von Eckardstein, Arnold
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146309/
https://www.ncbi.nlm.nih.gov/pubmed/33924941
http://dx.doi.org/10.3390/cells10051041
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author Robert, Jérôme
Osto, Elena
von Eckardstein, Arnold
author_facet Robert, Jérôme
Osto, Elena
von Eckardstein, Arnold
author_sort Robert, Jérôme
collection PubMed
description 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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spelling pubmed-81463092021-05-26 The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions Robert, Jérôme Osto, Elena von Eckardstein, Arnold Cells Review 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. MDPI 2021-04-28 /pmc/articles/PMC8146309/ /pubmed/33924941 http://dx.doi.org/10.3390/cells10051041 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Robert, Jérôme
Osto, Elena
von Eckardstein, Arnold
The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions
title The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions
title_full The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions
title_fullStr The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions
title_full_unstemmed The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions
title_short The Endothelium Is Both a Target and a Barrier of HDL’s Protective Functions
title_sort endothelium is both a target and a barrier of hdl’s protective functions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146309/
https://www.ncbi.nlm.nih.gov/pubmed/33924941
http://dx.doi.org/10.3390/cells10051041
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