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.
Chylomicron-remnant-like particles modify production of vasoactive mediators by endothelial cells
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M. Evans, Y. Berhane, K.M. Botham, J. Elliott, C.P.D. Wheeler-Jones; Chylomicron-remnant-like particles modify production of vasoactive mediators by endothelial cells. Biochem Soc Trans 1 February 2004; 32 (1): 110–112. doi: https://doi.org/10.1042/bst0320110
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