Atherogenic concentrations of low-density lipoprotein enhance endothelial cell generation of epoxyeicosatrienoic acid products.
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Pritchard KA Jr, Wong PY, Stemerman MB
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Oncology
Internal/Family Medicine
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Internal/Family Medicine
Oncology
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volume
136
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0002-9440
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["Pritchard KA Jr, Wong PY, Stemerman MB","Cells, Cultured, Dose-Response Relationship, Drug, Endothelium, Vascular drug effects, Endothelium, Vascular metabolism, Humans, Hydroxyeicosatetraenoic Acids metabolism, Thrombin pharmacology, 8,11,14-Eicosatrienoic Acid metabolism, Endothelium, Vascular cytology, Fatty Acids, Unsaturated metabolism, Lipoproteins, LDL pharmacology","English","1990-06-01","The American journal of pathology","136"]
Description
To investigate the effects of protracted low-density lipoprotein (LDL) exposure on endothelial cell (EC) epoxyeicosatrienoic acid (EET) generation, human umbilical vein ECs were incubated in atherogenic concentrations of LDL (240 mg cholesterol per deciliter) (LDL-EC). After 4 days' incubation with LDL, EC were stimulated with human thrombin in the presence of 1-[14C]-arachidonic acid. Substantially more EET products were generated by LDL-ECs than by cells not exposed to high levels of LDL (C-EC). Thrombin stimulation caused LDL-EC to produce five- to eightfold more in 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET, with 14,15-EET as the major product. This is the first demonstration, to date, that EETs can be induced in EC. Metapyrone (SKF-525A) markedly inhibited EC EET generation, indicating a role for the cytochrome P-450 enzyme system in human EC arachidonic acid metabolism. One EET product, 14,15-EET, has been found to be chemotactic and to promote adhesion of U937 cells, a human monocytic lymphoma cell line, to EC. Thus, protracted exposure to atherogenic LDL concentrations increases the generation of chemotactic and adhesion factors (ie, 14,15-EET) after thrombin stimulation, possibly through the cytochrome P-450 enzyme system.
