Document Detail

Damage of guinea pig heart and arteries by a trioleate-enriched diet and of cultured cardiomyocytes by oleic acid.
MedLine Citation:
PMID:  20221399     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Mono-unsaturated fatty acids (MUFAs) like oleic acid have been shown to cause apoptosis of cultured endothelial cells by activating protein phosphatase type 2C alpha and beta (PP2C). The question arises whether damage of endothelial or other cells could be observed in intact animals fed with a trioleate-enriched diet.
METHODOLOGY/PRINCIPAL FINDINGS: Dunkin-Hartley guinea pigs were fed with a trioleate-enriched diet for 5 months. Advanced atherosclerotic changes of the aorta and the coronary arteries could not be seen but the arteries appeared in a pre-atherosclerotic stage of vascular remodelling. However, the weight and size of the hearts were lower than in controls and the number of apoptotic myocytes increased in the hearts of trioleate-fed animals. To confirm the idea that oleic acid may have caused this apoptosis by activation of PP2C, cultured cardiomyocytes from guinea pigs and mice were treated with various lipids. It was demonstrable that oleic acid dose-dependently caused apoptosis of cardiomyocytes from both species, yet, similar to previous experiments with cultured neurons and endothelial cells, stearic acid, elaidic acid and oleic acid methylester did not. The apoptotic effect caused by oleic acid was diminished when PP2C alpha and beta were downregulated by siRNA showing that PP2C was causally involved in apoptosis caused by oleic acid.
CONCLUSIONS/SIGNIFICANCE: The glycerol trioleate diet given to guinea pigs for 5 months did not cause marked atherosclerosis but clearly damaged the hearts by activating PP2C alpha and beta. The diet used with 24% (wt/wt) glycerol trioleate is not comparable to human diets. The detrimental role of MUFAs for guinea pig heart tissue in vivo is shown for the first time. Whether it is true for humans remains to be shown.
Josef Krieglstein; Tobias Kewitz; Uwe Kirchhefer; Oliver Hofnagel; Gabriele Weissen-Plenz; Michael Reinbold; Susanne Klumpp
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-08
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-11     Completed Date:  2011-01-11     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e9561     Citation Subset:  IM    
Institut für Pharmazeutische und Medizinische Chemie, Westfaelische Wilhelms-Universitaet, Muenster, Germany.
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MeSH Terms
Animal Feed*
Arteries / drug effects,  metabolism*
Fatty Acids, Monounsaturated / metabolism
Guinea Pigs
Heart / drug effects,  physiology*
Myocardium / metabolism*
Myocytes, Cardiac / drug effects*
Oleic Acid / pharmacology*
Phosphoprotein Phosphatases / metabolism
Protein Phosphatase 2 / metabolism
Triolein / pharmacology
Reg. No./Substance:
0/Fatty Acids, Monounsaturated; 112-80-1/Oleic Acid; 122-32-7/Triolein; EC Phosphatases; EC Phosphatase 2; EC phosphatase 2C

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