damage of guinea pig heart and arteries by a trioleate-enriched diet and of cultured cardiomyocytes by oleic acid豚鼠心脏和动脉的损害trioleate-enriched饮食和油酸的培养心肌细胞.pdfVIP

Damage of Guinea Pig Heart and Arteries by a Trioleate-Enriched Diet and of Cultured Cardiomyocytes by Oleic Acid 1 1 2 3 3 Josef Krieglstein *, Tobias Kewitz , Uwe Kirchhefer , Oliver Hofnagel , Gabriele Weißen-Plenz , Michael Reinbold1, Susanne Klumpp1 ¨ ¨ 1 Institut fur Pharmazeutische und Medizinische Chemie, Westfaelische Wilhelms-Universitaet, Muenster, Germany, 2 Institut fur Pharmakologie und Toxikologie, Universitaetsklinikum Muenster, Muenster, Germany, 3 Leibniz-Institut fuer Arterioskleroseforschung, Universitaetsklinikum Muenster, Muenster, Germany Abstract 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 a and b (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-depe