Journal
CARDIOVASCULAR RESEARCH
Volume 82, Issue 2, Pages 341-350Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvp004
Keywords
Myocytes; Cell culture; Energy metabolism; Angiotensin; Remodelling
Categories
Funding
- Swiss National Science Foundation [3200-067873, 3100B0109212/1]
- Swiss University Conference project 'Heart remodellling in Health and Disease'
- Swiss Heart Foundation
- Foundation 'Centre de Recherche Medicale Carlos et Elsie de Reuter'
- Foundation 'Valentine Gerbex-Bourget'
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Advanced heart failure is often associated with reduced myocardial fatty acid oxidation capacity. We have previously observed that failing hearts of mice with overexpression of angiotensinogen in the myocardium exhibit marked reduction of key regulatory proteins of fatty acid oxidation. In the present study, we determined whether exposure of adult rat cardiac (ARC) myocytes to angiotensin II (Ang II) influences expression of fatty acid translocase, muscle-type carnitine palmitoyl transferase-I, and medium-chain acyl-CoA dehydrogenase. Ang II reduced mRNA expression of the three regulatory proteins in ARC myocytes during the entire 14-days culture period. However, protein expression and palmitate oxidation rate remained unaltered for 7 days, but subsequently markedly decreased. The decrease of protein expression and of fatty acid oxidation coincided with the onset of increased protein expression of tumour necrosis factor-alpha (TNF-alpha). The effect of Ang II was completely abolished by either blocking TNF-alpha formation through inhibition of reactive oxygen species-mediated activation of nuclear factor-kappa B or by neutralizing TNF-alpha with a specific antibody. Activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) and PPAR beta/delta counteracted Ang II-mediated reduction of the fatty acid oxidation pathway. Prolonged exposure of cardiac myocytes to Ang II elicits downregulation of the fatty acid oxidation pathway mediated by enhanced synthesis of TNF-alpha.
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