Division of Cardiovascular Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan.
Mol Nutr Food Res. 2015 Apr;59(4):729-40. doi: 10.1002/mnfr.201400537. Epub 2015 Jan 27.
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.
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.
TFA aggravates the antithrombogenic phenotypes of vascular endothelial cells via Toll-like receptors and promotes thrombus formation in mice.
由于摄入过多反式脂肪酸（TFA）会增加心肌梗死的风险，我们通过动物和细胞培养实验研究了 TFA 对血栓形成的影响。
将 C57BL/6 小鼠用含有 TFA 或顺式脂肪酸（总热量的 5%）或标准饮食喂养 4 周，并通过氦氖激光照射颈动脉诱导血栓形成。与标准饮食或顺式脂肪酸饮食相比，高 TFA 饮食显著促进了颈动脉中的血栓形成。TFA 在培养的内皮细胞和小鼠中激活了炎症信号通路；主动脉中抗血栓形成分子，包括血栓调节蛋白和组织因子途径抑制剂的基因表达水平降低，而 TFA 处理的小鼠中促血栓形成分子的表达水平升高。TFA 可显著上调促血栓形成分子，下调内皮细胞中的抗血栓形成分子。此外，TFA 诱导 c-Jun N 末端激酶、细胞外信号调节激酶和核因子-κB 的磷酸化。Toll 样受体 2 和 4 的遗传或药理学失活可抑制 TFA 激活的信号通路和内皮细胞的促血栓形成表型变化。
TFA 通过 Toll 样受体加重血管内皮细胞的抗血栓形成表型，并促进小鼠血栓形成。
