Vascular endothelial cell activation and dysfunction are critical early events in atherosclerosis. Selected dietary lipids (eg, fatty acids) may be atherogenic by activating endothelial cells and by potentiating an inflammatory response. Due to their prooxidant property, unsaturated fatty acids may play a critical role in endothelial cell activation and injury. To test this hypothesis, porcine endothelial cells were exposed to 18-carbon fatty acids differing in the degree of unsaturation, ie, 90 μmol/L stearic (18:0), oleic (18:1 n-9), linoleic (18:2n-6), or linolenic acid (18:3n-3) for 6 to 24 hours and/or tumor necrosis factor alpha ([TNF-α] 500 U/L) for up to 3 hours. Compared with control cultures, treatment with 18:0 and 18:2 decreased glutathione levels, suggesting an increase in cellular oxidative stress. Both 18:2 and 18:0 activated the transcription factor nuclear factor KB (NF-κB) the most and 18:1 the least. This NF-κB-dependent transcription was confirmed in endothelial cells by luciferase reporter gene assay. The fatty acid-mediated activation of NF-κB was blocked by preenrichment of the cultures with 25 κmol/L vitamin E. All fatty acids except 18:1 and 18:3 increased transendothelial albumin transfer, and 18:2 caused the most marked disruption of endothelial integrity. Preenrichment of endothelial cells with 18:2 followed by exposure to TNF-α resulted in a 100% increase in interleukin-6 (IL-6) production compared with TNF-α exposure alone. In contrast, cellular preenrichment with 18:0, 18:1, or 18:3 had no effect on TNF-α-mediated production of IL-6. Cellular release of radiolabeled arachidonic acid (20:4) was markedly increased only by cell exposure to 18:2 and 18:3, and the release of 20:4 appeared to be mainly from the phosphatidylethanolamine fraction. These data suggest that oleic acid does not activate endothelial cells. Furthermore, linoleic acid and other omega-6 fatty acids appear to be the most proinflammatory and possibly atherogenic fatty acids. Copyright (C) 2000 by W.B. Saunders Company.
|Number of pages||8|
|Journal||Metabolism: Clinical and Experimental|
|State||Published - 2000|
Bibliographical noteFunding Information:
From the Departments of Nutrition and Food Science and Neurosurgery, University of Kentucky, Lexington, KY; and Food Science Department, Purdue University, West Lafayette, IN. Submitted August 26, 1999; accepted January 24, 2000. Supported in part by grants from the National Institute of Environmental Health Sciences/Environmental Protection Agency, National Research Institute Competitive Grants Program/US Department of Agriculture, Department of Defense, National Cattleman’s Beef Association, American Heart Association Kentucky Affıliate, and the Kentucky Agricultural Experimental Station. Address reprint requests to Bernhard Hennig, PhD, Cell Nutrition Group, Department of Nutrition and Food Science, 204 Funkhouser Building, University of Kentucky, Lexington, KY 40506-0054. Copyright r 2000 by W.B. Saunders Company 0026-0495/00/4908-0020$10.00/0 doi:10.1053/meta.2000.7736
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism