Disturbed cardiac mitochondrial and cytosolic calcium handling in a metabolic risk-related rat model of heart failure with preserved ejection fraction
| العنوان: | Disturbed cardiac mitochondrial and cytosolic calcium handling in a metabolic risk-related rat model of heart failure with preserved ejection fraction |
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| المؤلفون: | Inês Falcão-Pires, Daniela Miranda-Silva, Patrícia Gonçalves-Rodrigues, Glória Conceição, Diederik W. D. Kuster, Alexandre Gonçalves, Ger J.M. Stienen, Jolanda van der Velden, Rob C. I. Wüst, Nádia Gonçalves, Adelino F. Leite-Moreira, Jorge Beleza, José Magalhães |
| المساهمون: | Physiology, ACS - Heart failure & arrhythmias, AMS - Ageing and Morbidity, Physics of Living Systems, Laboratory Genetic Metabolic Diseases, ACS - Diabetes & metabolism, AMS - Ageing & Morbidty |
| المصدر: | Acta Physiologica, 228(3):e13378. Wiley-Blackwell Miranda-Silva, D, Wüst, R C I, Conceição, G, Gonçalves-Rodrigues, P, Gonçalves, N, Gonçalves, A, Kuster, D W D, Leite-Moreira, A F, van der Velden, J, de Sousa Beleza, J M, Magalhães, J, Stienen, G J M & Falcão-Pires, I 2020, ' Disturbed cardiac mitochondrial and cytosolic calcium handling in a metabolic risk-related rat model of heart failure with preserved ejection fraction ', Acta Physiologica, vol. 228, no. 3, e13378, pp. e13378 . https://doi.org/10.1111/apha.13378 Acta physiologica (Oxford, England), 228(3):e13378. Wiley-Blackwell Miranda-Silva, D, Wüst, R C I, Conceição, G, Gonçalves-Rodrigues, P, Gonçalves, N D, Gonçalves, A, Kuster, D W D, Leite-Moreira, A F, van der Velden, J, de Sousa Beleza, J M, Magalhães, J, Stienen, G J M & Falcão-Pires, I 2020, ' Disturbed cardiac mitochondrial and cytosolic calcium handling in a metabolic risk-related rat model of heart failure with preserved ejection fraction ', Acta Physiologica, vol. 228, no. 3, e13378 . https://doi.org/10.1111/apha.13378 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, heart failure with preserved ejection fraction, Male, medicine.medical_specialty, cardiac muscle, Physiology, chemistry.chemical_element, 030204 cardiovascular system & hematology, Nicotinamide adenine dinucleotide, Mitochondrion, Calcium, Mitochondria, Heart, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cytosol, Internal medicine, medicine, Animals, Obesity, Cells, Cultured, Heart Failure, Metabolic Syndrome, Cardiac muscle, Stroke Volume, Phospholamban, Rats, Rats, Zucker, mitochondria, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, chemistry, Mitochondrial permeability transition pore, Heart failure with preserved ejection fraction |
| الوصف: | AIM: Calcium ions play a pivotal role in matching energy supply and demand in cardiac muscle. Mitochondrial calcium concentration is lower in animal models of heart failure with reduced ejection fraction (HFrEF), but limited information is available about mitochondrial calcium handling in heart failure with preserved ejection fraction (HFpEF).METHODS: We assessed mitochondrial Ca2+ handling in intact cardiomyocytes from Zucker/fatty Spontaneously hypertensive F1 hybrid (ZSF1)-lean (control) and ZSF1-obese rats, a metabolic risk-related model of HFpEF. A mitochondrially targeted Ca2+ indicator (MitoCam) was expressed in cultured adult rat cardiomyocytes. Cytosolic and mitochondrial Ca2+ transients were measured at different stimulation frequencies. Mitochondrial respiration and swelling, and expression of key proteins were determined ex vivo.RESULTS: At rest, mitochondrial Ca2+ concentration in ZSF1-obese was larger than in ZSF1-lean. The diastolic and systolic mitochondrial Ca2+ concentrations increased with stimulation frequency, but the steady-state levels were larger in ZSF1-obese. The half-widths of the contractile responses, the resting cytosolic Ca2+ concentration and the decay half-times of the cytosolic Ca2+ transients were higher in ZSF1-obese, likely because of a lower SERCA2a/phospholamban ratio. Mitochondrial respiration was lower, particularly with nicotinamide adenine dinucleotide (NADH) (complex I) substrates, and mitochondrial swelling was larger in ZSF1-obese.CONCLUSION: The free mitochondrial calcium concentration is higher in HFpEF owing to alterations in mitochondrial and cytosolic Ca2+ handling. This coupling between cytosolic and mitochondrial Ca2+ levels may compensate for myocardial ATP supply in vivo under conditions of mild mitochondrial dysfunction. However, if mitochondrial Ca2+ concentration is sustainedly increased, it might trigger mitochondrial permeability transition pore opening. |
| اللغة: | English |
| تدمد: | 1748-1708 |
| DOI: | 10.1111/apha.13378 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1896ab6103d7bcb7cd97e8d047e31a8a https://hdl.handle.net/1871.1/2e07a1ff-c228-40e9-9a34-4890ca383667 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1896ab6103d7bcb7cd97e8d047e31a8a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17481708 |
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| DOI: | 10.1111/apha.13378 |