Authors
Christina Christoffersen, Hideru Obinata, Sunil B Kumaraswamy, Sylvain Galvani, Josefin Ahnström, Madhumati Sevvana, Claudia Egerer-Sieber, Yves A Muller, Timothy Hla, Lars B Nielsen, Björn Dahlbäck
Publication date
2011/6/7
Journal
Proceedings of the National Academy of Sciences
Volume
108
Issue
23
Pages
9613-9618
Publisher
National Academy of Sciences
Description
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-Å 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 S1P1 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 …
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Scholar articles
C Christoffersen, H Obinata, SB Kumaraswamy… - Proceedings of the National Academy of Sciences, 2011