A mechanism by which dietary trans fats cause atherosclerosis

Dietary trans fats (IFS) have been causally linked to atherosclerosis, but the mechanism by which they cause the disease remains elusive. Suppressed transforming growth factor (TGF)-beta 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-beta 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-beta responsiveness in aortic endothelium. The suppressed TGF-beta responsiveness is evidenced by markedly reduced expression of TGF-beta type I and II receptors and profoundly decreased levels of phosphorylated Smad2, an important TGF-beta 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-beta responsiveness. This effect is presumably mediated by the increased deposition of cholesterol into cellular plasma membranes in vascular tissue, as in hypercholesterolemia. (C) 2011 Elsevier Inc. All rights reserved.