Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury
| العنوان: | Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury |
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| المؤلفون: | Liyan Zhang, Phing-How Lou, Petra C. Kienesberger, Michael Zaugg, Eliana Lucchinetti, Alexander S. Clanachan, Andreas Affolter, Markus Heck, Manoj Gandhi, Martin Hersberger |
| المساهمون: | University of Zurich, Zaugg, Michael |
| المصدر: | Cardiovascular Research. 97:251-261 |
| بيانات النشر: | Oxford University Press (OUP), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Methyl Ethers, medicine.medical_specialty, Physiology, Citric Acid Cycle, Myocardial Infarction, Respiratory chain, Myocardial Reperfusion Injury, 610 Medicine & health, Biology, 2705 Cardiology and Cardiovascular Medicine, Rats, Sprague-Dawley, Sevoflurane, chemistry.chemical_compound, 2737 Physiology (medical), Physiology (medical), Internal medicine, medicine, Animals, PPAR alpha, Carnitine, Ischemic Preconditioning, Beta oxidation, Triglycerides, Palmitoylcarnitine, chemistry.chemical_classification, Ventricular Remodeling, Myocardium, Fatty Acids, RNA-Binding Proteins, Fatty acid, 1314 Physiology, Hypoxia-Inducible Factor 1, alpha Subunit, Pyruvate dehydrogenase complex, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Mitochondria, Rats, Citric acid cycle, Endocrinology, chemistry, Biochemistry, 10036 Medical Clinic, Ischemic preconditioning, Energy Metabolism, Cardiology and Cardiovascular Medicine, Oxidation-Reduction, Transcription Factors, medicine.drug |
| الوصف: | Aims Infarct-remodelled hearts are less amenable to protection against ischaemia/reperfusion. Understanding preservation of energy metabolism in diseased vs. healthy hearts may help to develop anti-ischaemic strategies effective also in jeopardized myocardium. Methods and results Isolated infarct-remodelled/sham Sprague–Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischaemia and 30 min of reperfusion. Protection of post-ischaemic ventricular work was achieved by pharmacological conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [3H]palmitate and [14C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibres. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, the hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodelling and limited respiratory chain and citric acid cycle capacity. Unprotected remodelled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischaemia/reperfusion, which normalized in sevoflurane-protected remodelled hearts. Protected remodelled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibres and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodelled hearts exhibited higher PPARα-PGC-1α but defective HIF-1α signalling, and conditioning enabled them to mobilize fatty acids from endogenous triglyceride stores, which closely correlated with improved recovery. Conclusions Protected infarct-remodelled hearts secure post-ischaemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride stores. |
| وصف الملف: | Lou_Cardiovascular_Res_2013.pdf - application/pdf |
| تدمد: | 1755-3245 0008-6363 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9bd5f8512ddd94ed00ac37b254639ec0Test https://doi.org/10.1093/cvr/cvs323Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9bd5f8512ddd94ed00ac37b254639ec0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17553245 00086363 |
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