Abstract | BACKGROUND: METHODS AND RESULTS: Cardiac substrate uptake and oxidation were measured in 8 conscious, chronically instrumented dogs with decompensated pacing-induced heart failure and in 8 normal dogs by infusing 3 isotopically labeled substrates: 3H-oleate, 14C-glucose, and 13C-lactate. Although myocardial O2 consumption was not different between the 2 groups, the rate of oxidation of FFA was lower (2.8+/-0.6 versus 4.7+/-0.3 micromol x min(-1) x 100g(-1)) and of glucose was higher (4.6+/-1.0 versus 1.8+/-0.5 micromol x min(-1) x 100g(-1)) in failing compared with normal hearts (P<0.05). The rates of lactate uptake and lactate output were not significantly different between the 2 groups. In left ventricular tissue from failing hearts, the activity of 2 key enzymes of FFA oxidation was significantly reduced: carnitine palmitoyl transferase-I (0.54+/-0.04 versus 0.66+/-0.04 micromol x min(-1) x g(-1)) and medium chain acyl-coenzyme A dehydrogenase (MCAD; 1.8+/-0.1 versus 2.9+/-0.3 micromol x min(-1) x g(-1)). Consistently, the protein expression of MCAD and of RXRalpha were significantly reduced by 38% in failing hearts, but the expression of PPARalpha was not different. Moreover, there were significant correlations between the expression of RXRalpha and the expression and activity of MCAD. CONCLUSIONS: Our results provide the first evidence for a link between the reduced expression of RXRalpha and the switch in metabolic phenotype in severe heart failure.
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Authors | Juan Carlos Osorio, William C Stanley, Axel Linke, Michele Castellari, Quy N Diep, Ashish R Panchal, Thomas H Hintze, Gary D Lopaschuk, Fabio A Recchia |
Journal | Circulation
(Circulation)
Vol. 106
Issue 5
Pg. 606-12
(Jul 30 2002)
ISSN: 1524-4539 [Electronic] United States |
PMID | 12147544
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Carbon Isotopes
- Carbon Radioisotopes
- Fatty Acids
- Protein Isoforms
- Receptors, Cytoplasmic and Nuclear
- Receptors, Retinoic Acid
- Retinoid X Receptors
- Transcription Factors
- Tritium
- Oleic Acid
- Lactic Acid
- Fatty Acid Desaturases
- Acyl-CoA Dehydrogenase
- Carnitine O-Palmitoyltransferase
- Carboxy-Lyases
- malonyl-CoA decarboxylase
- Acetyl-CoA Carboxylase
- Glucose
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Topics |
- Acetyl-CoA Carboxylase
(analysis)
- Acyl-CoA Dehydrogenase
- Animals
- Carbon Isotopes
- Carbon Radioisotopes
- Carboxy-Lyases
(analysis)
- Cardiac Pacing, Artificial
- Carnitine O-Palmitoyltransferase
(analysis)
- Disease Models, Animal
- Dogs
- Enzyme Activation
- Fatty Acid Desaturases
(analysis)
- Fatty Acids
(metabolism)
- Glucose
(metabolism, pharmacokinetics)
- Heart Failure
(metabolism, pathology)
- Hemodynamics
- Lactic Acid
(metabolism, pharmacokinetics)
- Male
- Mitochondria, Heart
(enzymology)
- Myocardium
(chemistry, metabolism, pathology)
- Oleic Acid
(metabolism, pharmacokinetics)
- Oxidation-Reduction
- Protein Isoforms
(metabolism)
- Receptors, Cytoplasmic and Nuclear
(analysis, metabolism)
- Receptors, Retinoic Acid
(analysis, metabolism)
- Retinoid X Receptors
- Transcription Factors
(analysis, metabolism)
- Tritium
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