Trans fatty acids induce apoptosis in human endothelial cells.
The present study was designed to investigate the hypothesis that trans fatty acids can induce apoptosis of human umbilical vein endothelial cells (HUVEC). To test this hypothesis apoptosis was measured in HUVEC treated with 0.1, 1.0 or 5.0 mM trans elaidic acid (t-18:1) or linoelaidic acid (t,t-18:2) for 24 hours. For the detection of apoptosis, TdT-mediated dUTP nick end labelling assay (TUNEL), cell binding of annexin V and propidium iodide uptake were measured. Active Caspase-3 and cleaved PARP (poly-ADP-ribose polymerase) were also measured in the cell lysate. Moreover, cellular ability to produce ROS (reactive oxygen species) was measured by DCF fluorescence Both acids studied induce both early (annexin-positive cells) and late stages of apoptosis (cells stained by propidium iodide) in a dose-dependent manner. Also the appearance of TUNEL-positive cells was induced by both trans fatty acids tested, in a dose dependent manner. Both trans acids induce apoptosis through their effect on Caspase-3 activity and on intracellular ROS production. It is worth emphasising that linoelaidic acid proved to be a more potent inducer of apoptosis and ROS production in endothelial cells than elaidic acid. The present studies suggest that trans fatty acids may play a role in damaging and death of vascular endothelial cells in atherosclerosis.
Zapolska-Downar
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National Food and Nutrition Institute and Department of Biochemistry and Clinical Chemistry, Medical University, Warsaw, Poland.
Kośmider
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Naruszewicz
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D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D019301:Oleic Acid / Q000494:pharmacology; D009829:Oleic Acids; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044242:Trans Fatty Acids / Q000494:pharmacology*
D009829:Oleic Acids; D017382:Reactive Oxygen Species; D044242:Trans Fatty Acids; D019301:Oleic Acid; C011459:elaidic acid; D019787:Linoleic Acid; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3