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Atherogenic concentrations of low-density lipoprotein enhance endothelial cell generation of epoxyeicosatrienoic acid products. Am J Pathol 1990 Jun;136(6):1383-91

Date

06/01/1990

Pubmed ID

2356865

Pubmed Central ID

PMC1877592

Scopus ID

2-s2.0-0025334538   51 Citations

Abstract

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.

Author List

Pritchard KA Jr, Wong PY, Stemerman MB

Author

Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Cells, Cultured
Dose-Response Relationship, Drug
Endothelium, Vascular
Fatty Acids, Unsaturated
Humans
Hydroxyeicosatetraenoic Acids
Lipoproteins, LDL
Thrombin
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a