Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M Academic Article uri icon

Overview

MeSH Major

  • Apolipoproteins
  • Endothelium, Vascular
  • Lipoproteins, HDL
  • Lysophospholipids
  • Sphingosine

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-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 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.

publication date

  • June 7, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3111292

Digital Object Identifier (DOI)

  • 10.1073/pnas.1103187108

PubMed ID

  • 21606363

Additional Document Info

start page

  • 9613

end page

  • 8

volume

  • 108

number

  • 23