Abstract 10566: Trans-fatty Acid Accelerates Thrombus Formation In Vivo Through Aggravating Anti-thrombogenic Phenotype of Vascular Endothelial Cells
Purpose: Epidemiological studies revealed that excessive intake of trans-fatty acids (TFA) increase the risk of myocardial infarction. However, the role of TFA in thrombus formation has been incompletely elucidated. We aimed to investigate the effect of TFA on thrombus formation in vitro and in vivo.
Methods: C57BL6 mice were fed with diet-containing TFA (2% elaidic acid), cis-fatty acid (2% oleic acid) or normal chow diet for 4 weeks, and thrombus formation was induced in the carotid artery by He-Ne laser irradiation. Human umbilical vein endothelial cells (HUVEC) were treated with TFA or oleic acid. Gene expressions of thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), tissue factor (TF), and tumor necrosis factor-α (TNF-α) were evaluated by real-time PCR. Also, phosphorylation of toll-like receptor (TLR)-mediated intracellular signals was evaluated by Western blotting.
Results: Treatment of mice with high TFA diet significantly promoted He-Ne laser-induced thrombus formations in the carotid artery compared to chow diet and cis-fatty acid diet. Plasma total cholesterol, prothrombin time, and activated partial thromboplastin time were similar among three groups. Aortic expressions of anti-thrombogenic molecules including TM and TFPI were decreased, and those of pro-thrombogenic genes including PAI-1, TF, and TNF-α were increased in TFA-treated mice compared to control mice. Consistently, TFA upregulated the pro-thrombogenic molecules and downregulated anti-thrombogenic molecules in HUVEC. Furthermore, the TFA treatment induced phosphorylation of JNK and ERK and NFκB. Pretreatment with TLR 2 and 4 inhibitors inhibited these signal pathways and attenuated the pro-thrombogenic gene induction by TFA.
Conclusion: TFA aggravate anti-thrombogenic phenotypes of vascular endothelial cells through the TLR pathway, and promote thrombus formation.
- © 2013 by American Heart Association, Inc.