A mechanism by which dietary trans fats cause atherosclerosis

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / chemically induced*
  • Atherosclerosis / pathology
  • Cholesterol / metabolism
  • Dietary Fats / adverse effects*
  • Dietary Fats / metabolism
  • Endothelium, Vascular / metabolism
  • Hypercholesterolemia / etiology
  • Liver / metabolism
  • Male
  • Membrane Microdomains / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Myocardium / metabolism
  • Receptors, Transforming Growth Factor beta / metabolism
  • Trans Fatty Acids / adverse effects*
  • Transforming Growth Factor beta / metabolism


  • Dietary Fats
  • Receptors, Transforming Growth Factor beta
  • Trans Fatty Acids
  • Transforming Growth Factor beta
  • Cholesterol