Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1985162
- author
- organization
- publishing date
- 2011
- 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}}, }