Chylomicron-remnant-like particles modify production of vasoactive mediators by endothelial cells.
Endothelial-cell dysfunction is a critical initiating event in the pathogenesis of atherosclerosis. Although there is evidence to suggest that chylomicron remnants (CMRs), lipoproteins derived from the diet, influence endothelial-cell function to generate a pro-atherogenic phenotype, the mechanisms involved remain undefined. We have examined the effects of CMR-like particles (CMR-LPs) on human endothelial-cell function, focusing on the cyclo-oxygenase (COX) and nitric oxide synthase (NOS) pathways. CMR-LPs strongly enhanced the expression of the inducible cyclo-oxygenase COX-2 and increased prostacyclin synthesis in a biphasic manner. Studies with the COX-2-selective inhibitor NS-398 confirmed the COX-2 dependency of the later increase in prostanoid production. Pre-incubation with CMR-LPs reduced basal and thrombin-stimulated cGMP generation, whereas expression of endothelial NOS was not modified by remnant treatment.
Evans
M
M
Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK. mevans@rvc.ac.uk
Berhane
Y
Y
Botham
K M
KM
Elliott
J
J
Wheeler-Jones
C P D
CP
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D002478:Cells, Cultured; D053298:Chylomicron Remnants; D002914:Chylomicrons / Q000737:chemistry* / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D053298:Chylomicron Remnants; D002914:Chylomicrons; D007527:Isoenzymes; D008565:Membrane Proteins; D015121:6-Ketoprostaglandin F1 alpha; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases