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Journal of Lipid Research, Vol. 47, 1219-1226, June 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Distinct modulation of angiotensin II-induced early left ventricular hypertrophic gene programming by dietary fat type

Gábor Földes^*, Szilvia Vajda, Zoltán Lakó-Futó^*, Balázs Sármán^*, Réka Skoumal^*, Mika Ilves, Rudolf deChâtel^*, István Karádi^**, Miklós Tóth^*, Heikki Ruskoaho^1, and István Leprán

^* First Department of Medicine, Semmelweis University, Budapest, Hungary
^** Third Department of Medicine, Semmelweis University, Budapest, Hungary
Department of Pharmacology and Pharmacotherapy, Szeged University, Szeged, Hungary
Department of Physiology, Biocenter Oulu, University of Oulu, Oulu, Finland
Departments of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Oulu, Finland

Published, JLR Papers in Press, March 28, 2006.

¹ To whom correspondence should be addressed. e-mail: 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 the hypertrophic process. Rats assigned for 4 weeks of high-oil, high-fat, or standard diet were subjected to angiotensin II (Ang II; 33 µg/kg/h, subcutaneous) or vehicle infusion for 24 h. The Ang II-induced increase in left ventricular mRNA levels of hypertrophy-associated genes was higher in rats fed the high-oil diet compared with the standard diet. Western blotting revealed that, in parallel with changes in gene expression, the high-oil diet increased c-Jun N-terminal kinase phosphorylation (P < 0.001). Ang II increased p38 mitogen-activated protein kinase (MAPK) phosphorylation in rats fed the high-fat diet (3-fold; P < 0.01). The increase in transcription factor activator protein-1 (AP-1) DNA binding activity in response to Ang II was higher in rats fed the high-oil diet compared with those fed the standard diet (P < 0.001). Ang II downregulated inducible nitric oxide synthase mRNA levels in fatty acid-supplemented groups compared with the standard diet group. These results show that dietary fat type modulates the early activation of hypertrophic genes in pressure-overloaded myocardium involving the distinct activation of AP-1 and MAPK signal transduction pathways.

Supplementary key words cardiac hypertrophy • fatty acids • signal transduction • mitogen-activated protein kinases

Abbreviations: Ang II, angiotensin II; ANP, atrial natriuretic peptide; AP-1, activator protein-1; AT₁, angiotensin II type 1 receptor; BNP, B-type natriuretic peptide; BW, body weight; eNOS, endothelial nitric oxide synthase; ERK, extracellular signal-regulated protein kinase; iNOS, inducible nitric oxide synthase; JNK, c-Jun N-terminal protein kinase; LVW, left ventricular weight; MAPK, mitogen-activated protein kinase; NF-B, nuclear factor B

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