High-Density Lipoprotein–Associated Apolipoprotein M Limits Endothelial Inflammation by Delivering Sphingosine-1-Phosphate to the Sphingosine-1-Phosphate Receptor 1
(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.
(Less)
- author
- Ruiz Garcia, Mario LU ; Frej, Cecilia LU ; Holmér, Andreas LU ; Guo, Li J. LU ; Tran, Sinh LU and Dahlbäck, Björn LU
- organization
- publishing date
- 2017-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Arteriosclerosis, Thrombosis, and Vascular Biology
- volume
- 37
- issue
- 1
- pages
- 118 - 129
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:27879252
- wos:000391850900017
- scopus:84996757788
- 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
- 2025-01-12 17:28:04
@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 = {{Lippincott Williams & Wilkins}},
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}},
doi = {{10.1161/ATVBAHA.116.308435}},
volume = {{37}},
year = {{2017}},
}