Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Doisy Research Center, St. Louis, MO 63104, USA.
J Nutr Biochem. 2011 Jul;22(7):649-55. doi: 10.1016/j.jnutbio.2010.05.004. Epub 2010 Oct 30.
Dietary trans fats (TFs) have been causally linked to atherosclerosis, but the mechanism by which they cause the disease remains elusive. Suppressed transforming growth factor (TGF)-β responsiveness in aortic endothelium has been shown to play an important role in the pathogenesis of atherosclerosis in animals with hypercholesterolemia. We investigated the effects of a high TF diet on TGF-β responsiveness in aortic endothelium and integration of cholesterol in tissues. Here, we show that normal mice fed a high TF diet for 24 weeks exhibit atherosclerotic lesions and suppressed TGF-β responsiveness in aortic endothelium. The suppressed TGF-β responsiveness is evidenced by markedly reduced expression of TGF-β type I and II receptors and profoundly decreased levels of phosphorylated Smad2, an important TGF-β response indicator, in aortic endothelium. These mice exhibit greatly increased integration of cholesterol into tissue plasma membranes. These results suggest that dietary TFs cause atherosclerosis, at least in part, by suppressing TGF-β responsiveness. This effect is presumably mediated by the increased deposition of cholesterol into cellular plasma membranes in vascular tissue, as in hypercholesterolemia.
膳食反式脂肪（TFs）已被确定与动脉粥样硬化有关，但它们导致疾病的机制仍不清楚。在高胆固醇血症动物中，主动脉内皮细胞中转化生长因子（TGF）-β反应性受抑制被认为在动脉粥样硬化的发病机制中起重要作用。我们研究了高脂 TF 饮食对主动脉内皮细胞 TGF-β反应性和胆固醇在组织中整合的影响。在这里，我们表明，正常小鼠喂食高脂 TF 饮食 24 周后，会出现动脉粥样硬化病变和主动脉内皮细胞 TGF-β反应性受抑制。这种 TGF-β反应性受抑制的证据是，主动脉内皮细胞中 TGF-β Ⅰ型和Ⅱ型受体的表达明显减少，磷酸化 Smad2 的水平显著降低，磷酸化 Smad2 是 TGF-β 反应的一个重要指标。这些小鼠表现出胆固醇大量整合到组织质膜中。这些结果表明，膳食 TF 通过抑制 TGF-β反应性至少部分导致动脉粥样硬化。这种作用可能是通过增加胆固醇在血管组织的细胞质膜中的沉积来介导的，就像在高胆固醇血症中一样。
