Trans-fatty acid promotes thrombus formation in mice by aggravating antithrombogenic endothelial functions via Toll-like receptors.
Trans-fatty acid promotes thrombus formation in mice by aggravating antithrombogenic endothelial functions via Toll-like receptors.
复制标题
反式脂肪酸通过 Toll 样受体增强抗血栓内皮功能，从而促进小鼠血栓形成。
DOI：
10.1002/mnfr.201400537
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发表时间：
2014
影响因子：
5.2
通讯作者：
Hirata K.
中科院分区：
文献类型：
--
作者：
Kondo K;Ishida T;Yasuda T;Nakajima H;Mori K;Tanaka N;Mori T;Monguchi T;Shinohara M;Irino Y;Toh R;Rikitake Y;Kiyomizu K;Tomiyama Y;Yamamoto J;Hirata K.
范围由于过量摄入反式脂肪酸（TFA）会增加心肌梗死的风险，我们使用动物和细胞培养实验研究了TFA对血栓形成的影响。方法和结果C57 BL/6小鼠喂食含有TFA或顺式脂肪酸（各占总热量的5%）的饮食或普通饮食4周，并通过He-Ne激光照射诱导颈动脉血栓形成。与顺式脂肪酸饲料相比，高TFA饲料显著促进了颈动脉血栓形成。在培养的内皮细胞和小鼠中，TFA激活了炎症信号通路;在TFA处理的小鼠中，抗血栓形成分子（包括血栓调节蛋白和组织因子通路抑制剂）的主动脉基因表达水平降低，促血栓形成分子的表达水平升高。TFA显著上调内皮细胞促血栓形成分子，下调抗血栓形成分子。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的基因或药物失活可抑制TFA激活的信号通路和内皮细胞的促血栓形成表型变化。结论TFA通过Toll样受体激活血管内皮细胞的抗血栓形成表型，促进小鼠血栓形成。
ScopeSince excessive intake oftrans‐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 resultsC57BL/6 mice were fed a diet containing TFA orcis‐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 orcis‐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.ConclusionTFA aggravates the antithrombogenic phenotypes of vascular endothelial cells via Toll‐like receptors and promotes thrombus formation in mice.