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Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M

Christoffersen, Christina; Obinata, Hideru; Kumaraswamy, Sunil LU ; Galvani, Sylvain; Ahnström, Josefin LU ; Sevvana, Madhumati; Egerer-Sieber, Claudia; Muller, Yves A.; Hla, Timothy and Nielsen, Lars B., et al. (2011) In Proceedings of the National Academy of Sciences 108(23). p.9613-9618
Abstract
Protection of the endothelium is provided by circulating sphingosine-1-phosphate(S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-angstrom structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial... (More)
Protection of the endothelium is provided by circulating sphingosine-1-phosphate(S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-angstrom structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial adherens junctions, whereas apoM(-) HDL did not. Importantly, lack of S1P in the HDL fraction of Apom(-/-) mice decreased basal endothelial barrier function in lung tissue. Our results demonstrate that apoM, by delivering S1P to the S1P(1) receptor on endothelial cells, is a vasculoprotective constituent of HDL. (Less)
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publication status
published
subject
keywords
endothelial function, crystal structure, sphingolipids, vascular, permeability, atherosclerosis
in
Proceedings of the National Academy of Sciences
volume
108
issue
23
pages
9613 - 9618
publisher
National Acad Sciences
external identifiers
  • wos:000291341400060
  • scopus:79959340773
ISSN
1091-6490
DOI
10.1073/pnas.1103187108
language
English
LU publication?
yes
id
312f1460-b808-456d-a7ce-d510e434e860 (old id 1985162)
date added to LUP
2011-07-01 10:24:50
date last changed
2017-11-19 03:15:06
@article{312f1460-b808-456d-a7ce-d510e434e860,
  abstract     = {Protection of the endothelium is provided by circulating sphingosine-1-phosphate(S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-angstrom structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial adherens junctions, whereas apoM(-) HDL did not. Importantly, lack of S1P in the HDL fraction of Apom(-/-) mice decreased basal endothelial barrier function in lung tissue. Our results demonstrate that apoM, by delivering S1P to the S1P(1) receptor on endothelial cells, is a vasculoprotective constituent of HDL.},
  author       = {Christoffersen, Christina and Obinata, Hideru and Kumaraswamy, Sunil and Galvani, Sylvain and Ahnström, Josefin and Sevvana, Madhumati and Egerer-Sieber, Claudia and Muller, Yves A. and Hla, Timothy and Nielsen, Lars B. and Dahlbäck, Björn},
  issn         = {1091-6490},
  keyword      = {endothelial function,crystal structure,sphingolipids,vascular,permeability,atherosclerosis},
  language     = {eng},
  number       = {23},
  pages        = {9613--9618},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M},
  url          = {http://dx.doi.org/10.1073/pnas.1103187108},
  volume       = {108},
  year         = {2011},
}