A Mechanism by Which Dietary Trans Fats Cause Atherosclerosis
Dietary trans fats have been causally linked to atherosclerosis but the mechanism by which they cause the disease remain elusive. Suppressed 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 trans-fat (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 P-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 trans fats causeatherosclerosis, 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.