Cell-derived apolipoprotein E (ApoE) particles inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells

A K Stannard, D R Riddell, S M Sacre, A D Tagalakis, C Langer, A von Eckardstein, P Cullen, T Athanasopoulos, G Dickson, J S Owen

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Sub-endothelial infiltration of monocytes occurs early in atherogenesis and is facilitated by cell adhesion molecules that are up-regulated on activated endothelium. Apolipoprotein E (apoE) helps protect against atherosclerosis, in part, because apoE particles secreted by macrophages have local beneficial effects at lesion sites. Here, we hypothesize that such protection includes anti-inflammatory actions and investigate whether cell-derived apoE can inhibit tumor necrosis factor-alpha-mediated up-regulation of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Two models were used to mimic endothelial exposure to macrophage-derived apoE. In the first, HUVECs were transiently transfected to secrete apoE; VCAM-1 induction inversely correlated with secretion of apoE into the media (r = -0.76, p < 0.001). In the second, incubation of HUVECs with media from recombinant Chinese hamster ovary (CHO) cells expressing apoE (CHO(apoE)) also reduced VCAM-1 in a dose-dependent manner (r = -0.70, p < 0.001). Characterization of CHO(apoE) cell-derived apoE revealed several similarities to apoE particles secreted by human blood monocyte-derived macrophages. The suppression of endothelial activation by apoE most likely occurs via stimulation of endothelial nitric oxide synthase; apoE increased levels of intracellular nitric oxide and its surrogate marker, cyclic guanosine monophosphate, while the nitric oxide synthase inhibitor, ethyl-isothiourea, blocked its effect. We propose that apoE secreted locally at lesion sites by macrophages may be anti-inflammatory by stimulating endothelium to release NO and suppress VCAM-1 expression.

Original languageEnglish
Pages (from-to)46011-6
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number49
DOIs
Publication statusPublished - 5 Oct 2001

Keywords

  • Animals
  • Apolipoproteins E/physiology
  • CHO Cells
  • Cricetinae
  • Down-Regulation/physiology
  • Endothelium, Vascular/cytology
  • Humans
  • Nitric Oxide/metabolism
  • Transfection
  • Vascular Cell Adhesion Molecule-1/genetics

Fingerprint Dive into the research topics of 'Cell-derived apolipoprotein E (ApoE) particles inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells'. Together they form a unique fingerprint.

Cite this