alexa Trans-fatty acid promotes thrombus formation in mice by aggravating antithrombogenic endothelial functions via Toll-like receptors.


Journal of Nutrition & Food Sciences

Author(s): Kondo K, Ishida T, Yasuda T, Nakajima H, Mori K,

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Abstract SCOPE: Since excessive intake of trans-fatty acid (TFA) increases the risk of myocardial infarction, we investigated the effects of TFA on thrombus formation using animal and cell culture experiments. METHODS AND RESULTS: C57BL/6 mice were fed a diet containing TFA or cis-fatty acid (5\% each of total calories) or a chow diet for 4 weeks, and thrombus formation was induced in the carotid artery by He-Ne laser irradiation. The high-TFA diet significantly promoted thrombus formation in the carotid artery compared to the chow or cis-fatty acid diet. TFA activated the inflammatory signaling pathway in cultured endothelial cells and in mice; aortic gene expression levels of antithrombogenic molecules, including thrombomodulin and tissue factor pathway inhibitor, were decreased, and the expression levels of prothrombogenic molecules were increased in TFA-treated mice. TFA markedly upregulated the prothrombogenic molecules and downregulated the antithrombogenic molecules in endothelial cells. In addition, TFA induced phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and nuclear factor-κB. The TFA-activated signal pathways and prothrombogenic phenotypic changes of endothelial cells were inhibited by genetic or pharmacological inactivation of Toll-like receptors 2 and 4. CONCLUSION: TFA aggravates the antithrombogenic phenotypes of vascular endothelial cells via Toll-like receptors and promotes thrombus formation in mice. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This article was published in Mol Nutr Food Res and referenced in Journal of Nutrition & Food Sciences

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