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2003 | 08 | 1 |

Tytuł artykułu

Peroxisome proliferator-activated receptor alpha is downregulated in the failing human heart

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Cardiac hypertrophy in humans is associated with a decrease in myocardial fatty acid β-oxidation (FAO) and accompanying alterations in metabolic gene expression. Flux through the cardiac FAO pathway, which is the principal source of energy production in the adult mammalian heart, is tightly controlled in accordance with energy demands. In rodents, the FAO pathway is under control of a nuclear peroxisome proliferator-activated receptor α (PPARα). We sought to delineate the molecular regulatory events involved in the energy substrate preference switch from fatty acids to glucose during cardiac hypertrophic growth in humans. We analysed the amount of PPARα protein in human cardiac tissue. PPARα protein level was measured in homogenates prepared from left ventricular biopsies taken from five control donor hearts and compared to the amount of this transcription factor in biopsies from five patients with compensated end-stage heart failure (HF) at the time of transplantation. Using Western blot analysis with a monoclonal antibody against human PPARα, we observed a significant decrease (54%) in the mean amount of PPARα in the group of HF patients compared to that in the donor tissue. This study indicates that the decrease in cardiac PPARα transcription factor gene expression observed in the failing human heart could play an important role in a reduction in fatty acid utilisation by the adult heart during cardiac hypertrophy.

Wydawca

-

Rocznik

Tom

08

Numer

1

Opis fizyczny

p.49-53.fig.

Twórcy

autor
  • Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland
autor

Bibliografia

  • 1.Kagaya, Y., Kanno, Y., Takeyama, D., Ishide, N., Maruyama, Y., Takahashi, T., Ido, T. and Takishima, T. Effects of long-term pressure overload on regional myocardial glucose and free fatty acid uptake in rats. A quantitative autoradiographic study. Circulation 81 (1990) 1353-1361.
  • 2.Sack, M.N., Rader, T.A., Park, S., Bastin, J., McCune, S.A. and Kelly, D.P. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 94 (1996) 2837-2842.
  • 3.Schoonjans, K., Staels, B. and Auwerx, J. The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochem. Biophys. Acta 1302 (1996) 93-109.
  • 4.Watanabe, K., Fujii, H., Takahashi, T., Kodama, M., Aizawa, Y., Ohta, Y., Ono, T., Hasegawa, G., Naito, M., Nakajima, T., Kamijo, Y., Gonzalez, F.J. and Aoyama, T. Constitutive regulation of cardiac fatty acid metabolism through peroxisome proliferator-activated receptor alpha associated with age-dependent cardiac toxicity. J. Biol. Chem. 275 (2000) 22293-22299.
  • 5.Barger, P.M., Brandt, J.M., Leone, T.C., Weinheimer, C.J. and Kelly, D.P. Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth. J. Clin. Invest. 105 (2000) 1723-1730.
  • 6.Brandt, J.M., Djouadi, F. and Kelly, D.P. Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha. J. Biol. Chem. 273 (1998) 23786-23792.
  • 7.Mascaro, C., Acosta, E., Ortiz, J.A., Marrero, P.F., Hegardt, F.G. and Haro, D. Control of human muscle-type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor. J. Biol. Chem. 273 (1998) 8560-8563.
  • 8.Razeghi, P., Young, M.E., Alcorn, J.L., Moravec, C.S., Frazier, O.H. and Taegtmeyer, H. Metabolic gene expression in fetal and failing human heart. Circulation 104 (2001) 2923-2931.

Typ dokumentu

Bibliografia

Identyfikatory

Identyfikator YADDA

bwmeta1.element.agro-article-9489573e-1bca-42f8-8702-98de87355d95
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