Angiotensin II downregulates the fatty acid oxidation pathway in adult rat cardiomyocytes via release of tumour necrosis factor-α

• Published in: Cardiovascular research 2009-05, Vol.82 (2), p.341-350
• Main Authors: Pellieux, Corinne, Montessuit, Christophe, Papageorgiou, Irène, Lerch, René
• Format: Article
• Language: English
• Subjects: Acyl-CoA Dehydrogenase - metabolism; Angiotensin; Angiotensin II - pharmacology; Animals; Carnitine O-Palmitoyltransferase - metabolism; Cell culture; Cells, Cultured; Energy metabolism; Fatty Acids - metabolism; Male; Myocytes; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Natriuretic Peptide, Brain - metabolism; NF-kappa B - metabolism; Oxidation-Reduction; PPAR alpha - metabolism; PPAR delta - metabolism; PPAR gamma - metabolism; PPAR-beta - metabolism; Rats; Rats, Inbred Strains; Reactive Oxygen Species - metabolism; Remodelling; Signal Transduction - drug effects; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvp004

Aims 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. Methods and results 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-α (TNF-α). The effect of Ang II was completely abolished by either blocking TNF-α formation through inhibition of reactive oxygen species-mediated activation of nuclear factor-κB or by neutralizing TNF-α with a specific antibody. Activation of peroxisome proliferator-activated receptor-α (PPARα) and PPARβ/δ counteracted Ang II-mediated reduction of the fatty acid oxidation pathway. Conclusion Prolonged exposure of cardiac myocytes to Ang II elicits downregulation of the fatty acid oxidation pathway mediated by enhanced synthesis of TNF-α.