Submitted on December 21, 2005
Revised on March 10, 2006
Accepted on March 28, 2006
Distinct modulation of angiotensin II-induced early left ventricular hypertrophic gene programming by dietary fat type
Gabor Foldes, Szilvia Vajda, Zoltan Lako-Futo, Balazs Sarman, Reka Skoumal, Mika Ilves, Rudolf deChatel, Istvan Karadi, Miklos Toth, Heikki Ruskoaho, and Istvan Lepran
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Oulu, Oulu 90014
Corresponding Author: heikki.ruskoaho{at}oulu.fi
Long-term dietary fatty acid intake alters the development of left ventricular hypertrophy, but the linking signaling pathways are unclear. We studied the role and underlying signaling mechanisms of dietary fat intake in the early phase of hypertrophic process. The rats assigned for 4 weeks of high oil, high fat, or standard diet were subjected to angiotensin II (33 
g·kg-1·h-1, sc) or vehicle infusions for 24 hours. The angiotensin II-induced increase in left ventricular mRNA levels of hypertrophy-associated genes was higher in rats fed high oil diet compared to standard diet. Western blotting revealed that in parallel with changes in gene expression, high oil diet increased c-Jun N-terminal kinase phosphorylation (P<0.001). Angiotensin II increased p38 MAP kinase phosphorylation in rats fed high fat diet (3-fold, P<0.01). The increase in AP-1 DNA binding activity in response to angiotensin II was higher in rats fed high oil diet compared to those fed standard diet (P<0.001). Angiotensin II downregulated inducible nitric oxide synthase mRNA levels in fatty acid supplemented groups compared to standard diet group. These results show that dietary fat type modulates the early activation of hypertrophic genes in pressure overloaded myocardium involving distinct activation of AP-1 and MAP kinase signal transduction pathways.
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