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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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organization
publishing date
type
Contribution to journal
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 Academy of Sciences
external identifiers
  • wos:000291341400060
  • scopus:79959340773
  • pmid:21606363
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
2016-04-01 10:42:41
date last changed
2022-05-13 19:09:35
@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}},
  keywords     = {{endothelial function; crystal structure; sphingolipids; vascular; permeability; atherosclerosis}},
  language     = {{eng}},
  number       = {{23}},
  pages        = {{9613--9618}},
  publisher    = {{National Academy of 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}},
  doi          = {{10.1073/pnas.1103187108}},
  volume       = {{108}},
  year         = {{2011}},
}