Trans‐fatty acid promotes thrombus formation in mice by aggravating antithrombogenic endothelial functions via Toll‐like receptors. Issue 4 (27th January 2015)

• Record Type: Journal Article
• Authors: Kondo, Kensuke; Ishida, Tatsuro; Yasuda, Tomoyuki; Nakajima, Hideto; Mori, Kenta; Tanaka, Nobuaki; Mori, Takeshige; Monguchi, Tomoko; Shinohara, Masakazu; Irino, Yasuhiro; Toh, Ryuji; Rikitake, Yoshiyuki; Kiyomizu, Kazunobu; Tomiyama, Yoshiaki; Yamamoto, Junichiro; Hirata, Ken‐ichi
• Is Part Of: Molecular nutrition & food research. Volume 59:Issue 4(2015:Apr.)
• Page Start: 729
• Page End: 740
• Publication Date: 2015-01-27
• Subjects: Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201400537
• Languages: English
• ISSNs: 1613-4125

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mnfr2322-sec-0010" sec-type="section"> <title>Scope</title> <p>Since excessive intake of <italic>trans</italic>‐fatty acid (TFA) increases the risk of myocardial infarction, we investigated the effects of TFA on thrombus formation using animal and cell culture experiments.</p> </sec> <sec id="mnfr2322-sec-0020" sec-type="section"> <title>Methods and results</title> <p>C57BL/6 mice were fed a diet containing TFA or <italic>cis</italic>‐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 <italic>cis</italic>‐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.</p> </sec> <sec id="mnfr2322-sec-0030" sec-type="section"> <title>Conclusion</title> <p>TFA aggravates the antithrombogenic phenotypes of vascular endothelial cells via Toll‐like receptors and promotes thrombus formation in mice.</p> </sec> </abstract>