Document Detail


A mechanism by which dietary trans fats cause atherosclerosis.
MedLine Citation:
PMID:  21036587     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Chun-Lin Chen; Laura H Tetri; Brent A Neuschwander-Tetri; Shuan Shian Huang; Jung San Huang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-30
Journal Detail:
Title:  The Journal of nutritional biochemistry     Volume:  22     ISSN:  1873-4847     ISO Abbreviation:  J. Nutr. Biochem.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-17     Completed Date:  2011-10-14     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  9010081     Medline TA:  J Nutr Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  649-55     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Atherosclerosis / chemically induced*,  pathology
Cholesterol / metabolism
Dietary Fats / adverse effects*,  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
Grant Support
ID/Acronym/Agency:
AR 052578/AR/NIAMS NIH HHS; HL 087463/HL/NHLBI NIH HHS; R41 HL087463/HL/NHLBI NIH HHS; R41 HL087463-01/HL/NHLBI NIH HHS; R43 AR052578/AR/NIAMS NIH HHS; R43 AR052578-01A1/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Dietary Fats; 0/Receptors, Transforming Growth Factor beta; 0/Trans Fatty Acids; 0/Transforming Growth Factor beta; 97C5T2UQ7J/Cholesterol
Comments/Corrections

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