Stannard, AK and Riddell, DR and Sacre, SM and Tagalakis, AD and Langer, C and von Eckardstein, A and Cullen, P and Athanasopoulos, T and Dickson, G and Owen, JS (2001) Cell-derived apolipoprotein E (ApoE) particles inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells. J BIOL CHEM , 276 (49) 46011 - 46016.
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 antiinflammatory actions and investigate whether cell-derived apoE can inhibit tumor necrosis factor-a-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 (CHOapoE) also reduced VCAM-1 in a dose-dependent manner (r = -0.70, p < 0.001). Characterization of CHOapoE 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.
|Title:||Cell-derived apolipoprotein E (ApoE) particles inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells|
|Open access status:||An open access publication|
|Keywords:||HUMAN-BLOOD-PLATELETS, NITRIC-OXIDE, LIPOPROTEIN METABOLISM, GENE-EXPRESSION, DEFICIENT MICE, VLDL RECEPTOR, ATHEROSCLEROSIS, MACROPHAGES, CHOLESTEROL, AGGREGATION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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