Trans fatty acids: induction of a pro-inflammatory phenotype in endothelial cells.
Epidemiological data have shown an association of the intake of industrial produced trans fatty acids (TFA) and sudden cardiac death. The present study examines the impact of elaidic acid (t18:1n-9) and linoelaidic acid (t18:2n-6) on the human aortic endothelial cell functional response. Trans fatty acids predominately incorporated into the phospholipid component while only a minute fraction of the total fatty acids (FA) incorporated into triacylglycerol. Trans fatty acids incorporated into the plasma membranes at the expense of the saturated-FA, stearic, palmitic, and to a lesser extent, myristic acid. Both t18:1n-9 and t18:2n-6 induced a pro-inflammatory response by elevating surface expression of intercellular adhesion molecule-1 (ICAM-1). Neither oleic nor linoleic evoked a pro-inflammatory phenotype under the maximal 50 µM treatments. Both TFA and stearic acid increased phosphorylation of the ICAM-1 transcriptional regulator, nuclear factor-κβ (NF-κβ), while oleic and linoleic acids did not appear to alter the phosphorylation status. Elaidic acid minimally affected endothelial cell growth, whereas linoelaidic acid completely inhibited growth at 100 µM and imparted limited cytotoxicity up to 300 µM. Stearic acid induced cytotoxicity at concentrations above 75 µM, while oleic and linoleic acids evoked gradual dose-dependent growth inhibition with cytotoxicity occurring only at linoleic acid concentrations greater than 200 µM. In conclusion, t18:1n-9 and t18:2n-6 fatty acids effectively incorporated into the phospholipid component of endothelial cells and subsequently induce a pro-inflammatory phenotype.
Cellular Biochemistry Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA.
Kevin A
KA
Harvey
Candace L
CL
Walker
Zhidong
Z
Xu
Phillip
P
Whitley
Rafat A
RA
Siddiqui
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology*; D019787:Linoleic Acid / Q000378:metabolism / Q000494:pharmacology; D019301:Oleic Acid / Q000378:metabolism / Q000494:pharmacology; D009829:Oleic Acids; D013229:Stearic Acids / Q000378:metabolism / Q000494:pharmacology; D044242:Trans Fatty Acids / Q000378:metabolism* / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D005227:Fatty Acids; D009829:Oleic Acids; D013229:Stearic Acids; D044242:Trans Fatty Acids; D014280:Triglycerides; D019301:Oleic Acid; C011459:elaidic acid; C031183:stearic acid; D019787:Linoleic Acid