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High-Density Lipoprotein–Associated Apolipoprotein M Limits Endothelial Inflammation by Delivering Sphingosine-1-Phosphate to the Sphingosine-1-Phosphate Receptor 1

Ruiz Garcia, Mario LU ; Frej, Cecilia LU ; Holmér, Andreas LU ; Guo, Li J. LU ; Tran, Sinh LU and Dahlbäck, Björn LU (2017) In Arteriosclerosis, Thrombosis, and Vascular Biology 37(1). p.118-129
Abstract

OBJECTIVE—: Plasma high-density lipoproteins (HDL) are potent antiatherogenic and anti-inflammatory particles. However, HDL particles are highly heterogenic in composition, and different HDL-mediated functions can be ascribed to different subclasses of HDL. Only a small HDL population contains apolipoprotein M (ApoM), which is the main plasma carrier of the bioactive lipid mediator sphingosine-1-phosphate (S1P). Vascular inflammation is modulated by S1P, but both pro- and anti-inflammatory roles have been ascribed to S1P. The goal of this study is to elucidate the role of ApoM and S1P in endothelial anti-inflammatory events related to HDL. APPROACH AND RESULTS—: Aortic or brain human primary endothelial cells were challenged with tumor... (More)

OBJECTIVE—: Plasma high-density lipoproteins (HDL) are potent antiatherogenic and anti-inflammatory particles. However, HDL particles are highly heterogenic in composition, and different HDL-mediated functions can be ascribed to different subclasses of HDL. Only a small HDL population contains apolipoprotein M (ApoM), which is the main plasma carrier of the bioactive lipid mediator sphingosine-1-phosphate (S1P). Vascular inflammation is modulated by S1P, but both pro- and anti-inflammatory roles have been ascribed to S1P. The goal of this study is to elucidate the role of ApoM and S1P in endothelial anti-inflammatory events related to HDL. APPROACH AND RESULTS—: Aortic or brain human primary endothelial cells were challenged with tumor necrosis factor-α (TNF-α) as inflammatory stimuli. The presence of recombinant ApoM-bound S1P or ApoM-containing HDL reduced the abundance of adhesion molecules in the cell surface, whereas ApoM and ApoM-lacking HDL did not. Specifically, ApoM-bound S1P decreased vascular adhesion molecule-1 (VCAM-1) and E-selectin surface abundance but not intercellular adhesion molecule-1. Albumin, which is an alternative S1P carrier, was less efficient in inhibiting VCAM-1 than ApoM-bound S1P. The activation of the S1P receptor 1 was sufficient and required to promote anti-inflammation. Moreover, ApoM-bound S1P induced the rearrangement of the expression of S1P-related genes to counteract TNF-α. Functionally, HDL/ApoM/S1P limited monocyte adhesion to the endothelium and maintained endothelial barrier integrity under inflammatory conditions. CONCLUSIONS—: ApoM-bound S1P is a key component of HDL and is responsible for several HDL-associated protective functions in the endothelium, including regulation of adhesion molecule abundance, leukocyte-endothelial adhesion, and endothelial barrier.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arteriosclerosis, Thrombosis, and Vascular Biology
volume
37
issue
1
pages
118 - 129
publisher
American Heart Association
external identifiers
  • scopus:84996757788
  • wos:000391850900017
ISSN
1079-5642
DOI
10.1161/ATVBAHA.116.308435
language
English
LU publication?
yes
id
1a19f675-eb87-45c1-b5d9-45f1d7ed87be
date added to LUP
2016-12-12 07:52:43
date last changed
2018-01-14 04:28:11
@article{1a19f675-eb87-45c1-b5d9-45f1d7ed87be,
  abstract     = {<p>OBJECTIVE—: Plasma high-density lipoproteins (HDL) are potent antiatherogenic and anti-inflammatory particles. However, HDL particles are highly heterogenic in composition, and different HDL-mediated functions can be ascribed to different subclasses of HDL. Only a small HDL population contains apolipoprotein M (ApoM), which is the main plasma carrier of the bioactive lipid mediator sphingosine-1-phosphate (S1P). Vascular inflammation is modulated by S1P, but both pro- and anti-inflammatory roles have been ascribed to S1P. The goal of this study is to elucidate the role of ApoM and S1P in endothelial anti-inflammatory events related to HDL. APPROACH AND RESULTS—: Aortic or brain human primary endothelial cells were challenged with tumor necrosis factor-α (TNF-α) as inflammatory stimuli. The presence of recombinant ApoM-bound S1P or ApoM-containing HDL reduced the abundance of adhesion molecules in the cell surface, whereas ApoM and ApoM-lacking HDL did not. Specifically, ApoM-bound S1P decreased vascular adhesion molecule-1 (VCAM-1) and E-selectin surface abundance but not intercellular adhesion molecule-1. Albumin, which is an alternative S1P carrier, was less efficient in inhibiting VCAM-1 than ApoM-bound S1P. The activation of the S1P receptor 1 was sufficient and required to promote anti-inflammation. Moreover, ApoM-bound S1P induced the rearrangement of the expression of S1P-related genes to counteract TNF-α. Functionally, HDL/ApoM/S1P limited monocyte adhesion to the endothelium and maintained endothelial barrier integrity under inflammatory conditions. CONCLUSIONS—: ApoM-bound S1P is a key component of HDL and is responsible for several HDL-associated protective functions in the endothelium, including regulation of adhesion molecule abundance, leukocyte-endothelial adhesion, and endothelial barrier.</p>},
  author       = {Ruiz Garcia, Mario and Frej, Cecilia and Holmér, Andreas and Guo, Li J. and Tran, Sinh and Dahlbäck, Björn},
  issn         = {1079-5642},
  language     = {eng},
  number       = {1},
  pages        = {118--129},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis, and Vascular Biology},
  title        = {High-Density Lipoprotein–Associated Apolipoprotein M Limits Endothelial Inflammation by Delivering Sphingosine-1-Phosphate to the Sphingosine-1-Phosphate Receptor 1},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.116.308435},
  volume       = {37},
  year         = {2017},
}