المؤلفون: Anne Berit Johnsen, Karin Garten, Eirik Skogvoll, Nathan R. Scrimgeour, Godfrey L. Smith, Øyvind Ellingsen, Kari Jørgensen, Bjarne M. Nes, Tomas Stølen, Julie R. McMullen, José Bianco Nascimento Moreira, Muhammad Shakil Ahmed, Ulrik Wisløff, Maria P. Hortigon-Vinagre, Håvard Attramadal, Anne Marie Ormbostad Berre, Morten A. Høydal, Victor Zamora

المصدر: Journal of Molecular and Cellular Cardiology. 148:106-119

مصطلحات موضوعية: 0301 basic medicine, Cardiac function curve, medicine.medical_specialty, Myocardial Infarction, Infarction, Cardiomegaly, 030204 cardiovascular system & hematology, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Endurance training, Physical Conditioning, Animal, Internal medicine, medicine, Animals, Aerobic exercise, Myocytes, Cardiac, Myocardial infarction, Molecular Biology, computer.programming_language, Heart Failure, sed, business.industry, Arrhythmias, Cardiac, medicine.disease, Myocardial Contraction, Aerobiosis, Electrophysiological Phenomena, MicroRNAs, Electrophysiology, 030104 developmental biology, Gene Expression Regulation, Heart failure, Ventricular Fibrillation, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, computer, Biomarkers

الوصف: Aims Endurance training improves aerobic fitness and cardiac function in individuals with heart failure. However, the underlying mechanisms are not well characterized. Exercise training could therefore act as a tool to discover novel targets for heart failure treatment. We aimed to associate changes in Ca2+ handling and electrophysiology with micro-RNA (miRNA) profile in exercise trained heart failure rats to establish which miRNAs induce heart failure-like effects in Ca2+ handling and electrophysiology. Methods and results Post-myocardial infarction (MI) heart failure was induced in Sprague Dawley rats. Rats with MI were randomized to sedentary control (sed), moderate (mod)- or high-intensity (high) endurance training for 8 weeks. Exercise training improved cardiac function, Ca2+ handling and electrophysiology including reduced susceptibility to arrhythmia in an exercise intensity-dependent manner where high intensity gave a larger effect. Fifty-five miRNAs were significantly regulated (up or down) in MI-sed, of which 18 and 3 were changed towards Sham-sed in MI-high and MI-mod, respectively. Thereafter we experimentally altered expression of these “exercise-miRNAs” individually in human induced pluripotent stem cell-derived cardiomyocytes (hIPSC-CM) in the same direction as they were changed in MI. Of the “exercise-miRNAs”, miR-214-3p prolonged AP duration, whereas miR-140 and miR-208a shortened AP duration. miR-497-5p prolonged Ca2+ release whereas miR-214-3p and miR-31a-5p prolonged Ca2+ decay. Conclusion Using exercise training as a tool, we discovered that miR-214-3p, miR-497-5p, miR-31a-5p contribute to heart-failure like behaviour in Ca2+ handling and electrophysiology and could be potential treatment targets.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fface9394415454ab86fc6645cfb38aeTest
https://doi.org/10.1016/j.yjmcc.2020.08.015Test

المؤلفون: Tomas Stølen, Øyvind Ellingsen, Morteza Esmaeili, Morten A. Høydal, Martin Wohlwend, Tone Frost Bathen, Mingshu Shi

المصدر: Scandinavian Cardiovascular Journal. 54:84-91

مصطلحات موضوعية: High-energy phosphate, medicine.medical_specialty, Phosphocreatine, medicine.medical_treatment, Cardiac metabolism, 030204 cardiovascular system & hematology, Mitochondria, Heart, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, Adenosine Triphosphate, Oxygen Consumption, 0302 clinical medicine, Internal medicine, medicine, Animals, 030212 general & internal medicine, Myocardial infarction, Heart Failure, Myocardial energetics, Exercise Tolerance, Rehabilitation, business.industry, Myocardium, VO2 max, medicine.disease, Exercise Therapy, Disease Models, Animal, chemistry, Heart failure, Cardiology, Female, Energy Metabolism, Cardiology and Cardiovascular Medicine, business, human activities, Biomarkers

الوصف: Objectives. Heart failure (HF) impairs resting myocardial energetics, myocardial mitochondrial performance, and maximal oxygen uptake (VO2max). Exercise training is included in most rehabilitation ...

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44f570087bc7939c27849e8508f91486Test
https://doi.org/10.1080/14017431.2019.1658893Test

المؤلفون: Simona Salerno, Paola Ceriotti, Linda H. Bergersen, Cecilie Morland, Morten A. Høydal, Tomas Stølen, Jon Storm-Mathisen, Daniele Catalucci, Fredrik Hjulstad Bækkerud

المصدر: Baekkerud, F H, Salerno, S, Ceriotti, P, Morland, C, Storm-Mathisen, J, Bergersen, L H, Hoydal, M A, Catalucci, D & Stolen, T O 2019, ' High Intensity Interval Training Ameliorates Mitochondrial Dysfunction in the Left Ventricle of Mice with Type 2 Diabetes ', Cardiovascular Toxicology, vol. 19, no. 5, pp. 422-431 . https://doi.org/10.1007/s12012-019-09514-zTest

مصطلحات موضوعية: Male, medicine.medical_specialty, Time Factors, Strength training, Diabetic Cardiomyopathies, Alpha (ethology), Oxidative phosphorylation, Diabetic cardiomyopathy, 030204 cardiovascular system & hematology, Mitochondrion, High-Intensity Interval Training, Toxicology, Interval training, Mitochondria, Heart, Ventricular Function, Left, Exercise training, 03 medical and health sciences, Ventricular Dysfunction, Left, 0302 clinical medicine, Endurance training, Internal medicine, Medicine, Animals, Molecular Biology, business.industry, Diabetes, medicine.disease, Mice, Mutant Strains, Mitochondria, Disease Models, Animal, Endocrinology, Diabetes Mellitus, Type 2, Gene Expression Regulation, 030220 oncology & carcinogenesis, Cardiology and Cardiovascular Medicine, business, Energy Metabolism, High-intensity interval training, Signal Transduction

الوصف: Both human and animal studies have shown mitochondrial and contractile dysfunction in hearts of type 2 diabetes mellitus (T2DM). Exercise training has shown positive effects on cardiac function, but its effect on the mitochondria have been insufficiently explored. The aim of this study was to assess the effect of exercise training on mitochondrial function in T2DM hearts. We divided T2DM mice (db/db) into a sedentary and an interval training group at 8 weeks of age and used heterozygote db/+ as controls. After 8 weeks of training, we evaluated mitochondrial structure and function, as well as the levels of mRNA and proteins involved in key metabolic processes from the left ventricle. db/db animals showed decreased oxidative phosphorylation capacity and fragmented mitochondria. Mitochondrial respiration showed a blunted response to Ca2+ along with reduced protein levels of the mitochondrial calcium uniporter. Exercise training ameliorated the reduced oxidative phosphorylation in complex (C) I + II, CII and CIV, but not CI or Ca2+ response. Mitochondrial fragmentation was partially restored. mRNA levels of isocitrate, succinate and oxoglutarate dehydrogenase were increased in db/db mice and normalized by exercise training. Exercise training induced an upregulation of two transcripts of peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α1 and PGC1α4) previously linked to endurance training adaptations and strength training adaptations, respectively. The T2DM heart showed mitochondrial dysfunction at multiple levels and exercise training ameliorated some, but not all mitochondrial dysfunctions.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9370ecd40d3a8c4effde6e2683869b40Test
https://pubmed.ncbi.nlm.nih.gov/30927207Test

المؤلفون: Øyvind Ellingsen, Morteza Esmaeili, Mingshu Shi, Tone Frost Bathen, Tomas Stølen, Morten A. Høydal

المصدر: Metabolites
Volume 9
Issue 3
9:53
Metabolites, Vol 9, Iss 3, p 53 (2019)

مصطلحات موضوعية: In vivo magnetic resonance spectroscopy, medicine.medical_specialty, Taurine, MRS, Endocrinology, Diabetes and Metabolism, Metabolite, lcsh:QR1-502, Hypotaurine, 030204 cardiovascular system & hematology, Biochemistry, lcsh:Microbiology, Article, 03 medical and health sciences, chemistry.chemical_compound, cardiac metabolism, 0302 clinical medicine, Internal medicine, Medicine, Molecular Biology, medicine.diagnostic_test, business.industry, Skeletal muscle, Magnetic resonance imaging, Metabolism, medicine.disease, metabolomics, magnetic resonance spectroscopy, medicine.anatomical_structure, Endocrinology, chemistry, Heart failure, business, 030217 neurology & neurosurgery

الوصف: he metabolism and performance of myocardial and skeletal muscle are impaired in heart failure (HF) patients. Exercise training improves the performance and benefits the quality of life in HF patients. The purpose of the present study was to determine the metabolic profiles in myocardial and skeletal muscle in HF and exercise training using MRS, and thus to identify targets for clinical MRS in vivo. After surgically establishing HF in rats, we randomized the rats to exercise training programs of different intensities. After the final training session, rats were sacrificed and tissues from the myocardial and skeletal muscle were extracted. Magnetic resonance spectra were acquired from these extracts, and principal component and metabolic enrichment analysis were used to assess the differences in metabolic profiles. The results indicated that HF affected myocardial metabolism by changing multiple metabolites, whereas it had a limited effect on skeletal muscle metabolism. Moreover, exercise training mainly altered the metabolite distribution in skeletal muscle, indicating regulation of metabolic pathways of taurine and hypotaurine metabolism and carnitine synthesis. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0ec84c4258df32d499ad0871066ac5f3Test
http://hdl.handle.net/11250/2639912Test

المؤلفون: Godfrey L. Smith, Simona Salerno, Tomas Stølen, Ole-Johan Kemi, Allen Kelly, Karin Garten, Iffath A. Ghouri

المصدر: Frontiers in Physiology
Frontiers in Physiology, Vol 9 (2018)

مصطلحات موضوعية: 0301 basic medicine, Physiology, Infarction, Connective tissue, 030204 cardiovascular system & hematology, lcsh:Physiology, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Two-photon excitation microscopy, border zone, Physiology (medical), Optical mapping, medicine, Myocardial infarction, two-photon microscopy, Original Research, intracellular calcium, CATS, lcsh:QP1-981, Chemistry, Correction, medicine.disease, Electrophysiology, optical mapping, 030104 developmental biology, medicine.anatomical_structure, myocardial infarction, Ventricle

الوصف: Background: The origin of electrical behavior in post-myocardial infarction scar tissue is still under debate. This study aims to examine the extent and nature of the residual electrical activity within a stabilized ventricular infarct scar. Methods and Results: An apical infarct was induced in the left ventricle of Wistar rats by coronary artery occlusion. Five weeks post-procedure, hearts were Langendorff-perfused, and optically mapped using di-4-ANEPPS. Widefield imaging of optical action potentials (APs) on the left ventricular epicardial surface revealed uniform areas of electrical activity in both normal zone (NZ) and infarct border zone (BZ), but only limited areas of low-amplitude signals in the infarct zone (IZ). 2-photon (2P) excitation of di-4-ANEPPS and Fura-2/AM at discrete layers in the NZ revealed APs and Ca2+ transients (CaTs) to 500–600 μm below the epicardial surface. 2P imaging in the BZ revealed superficial connective tissue structures lacking APs or CaTs. At depths greater than approximately 300 μm, myocardial structures were evident that supported normal APs and CaTs. In the IZ, although 2P imaging did not reveal clear myocardial structures, low-amplitude AP signals were recorded at discrete layers. No discernible Ca2+ signals could be detected in the IZ. AP rise times in BZ were slower than NZ (3.50 ± 0.50 ms vs. 2.23 ± 0.28 ms) and further slowed in IZ (9.13 ± 0.56 ms). Widefield measurements of activation delay between NZ and BZ showed negligible difference (3.37 ± 1.55 ms), while delay values in IZ showed large variation (11.88 ± 9.43 ms). Conclusion: These AP measurements indicate that BZ consists of an electrically inert scar above relatively normal myocardium. Discrete areas/layers of IZ displayed entrained APs with altered electrophysiology, but the structure of this tissue remains to be elucidated. Copyright © 2018 Ghouri, Kelly, Salerno, Garten, Stølen, Kemi and Smith. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d960c145d171c071d09422fc7daeea0eTest
https://eprints.gla.ac.uk/174594/7/174594.pdfTest

المؤلفون: Øyvind Ellingsen, Tone Frost Bathen, Tomas Stølen, Steven L. Britton, Mingshu Shi, Lauren G. Koch, Morten A. Høydal, Morteza Esmaeili, Ulrik Wisløff

المصدر: PLoS ONE
PLOS ONE
PLoS ONE, Vol 13, Iss 12, p e0208703 (2018)

مصطلحات موضوعية: 0301 basic medicine, Aging, Physiology, Proton Magnetic Resonance Spectroscopy, Glutamine, 030204 cardiovascular system & hematology, Biochemistry, Interval training, Running, Random Allocation, 0302 clinical medicine, Glucose Metabolism, Medicine and Health Sciences, Public and Occupational Health, Amino Acids, Musculoskeletal System, Multidisciplinary, Organic Compounds, Muscles, Acidic Amino Acids, Monosaccharides, Neurochemistry, Neurotransmitters, Sports Science, Chemistry, medicine.anatomical_structure, Physical Sciences, Medicine, Carbohydrate Metabolism, Glutamate, Anatomy, High-intensity interval training, Research Article, medicine.medical_specialty, Science, Carbohydrates, Carbohydrate metabolism, 03 medical and health sciences, Species Specificity, Internal medicine, medicine, Animals, Outbred Strains, Aerobic exercise, Animals, Sports and Exercise Medicine, Muscle, Skeletal, Exercise, Aerobic capacity, Soleus muscle, business.industry, Biological Locomotion, Organic Chemistry, Chemical Compounds, Skeletal muscle, Biology and Life Sciences, Proteins, Physical Activity, Soleus Muscles, Rats, 030104 developmental biology, Endocrinology, Metabolism, Glucose, Skeletal Muscles, Ageing, Physical Fitness, Physical Endurance, Sedentary Behavior, business, human activities, Neuroscience

الوصف: Purpose Exercise training increases aerobic capacity and is beneficial for health, whereas low aerobic exercise capacity is a strong independent predictor of cardiovascular disease and premature death. The purpose of the present study was to determine the metabolic profiles in a rat model of inborn low versus high capacity runners (LCR/HCR) and to determine the effect of inborn aerobic capacity, aging, and exercise training on skeletal muscle metabolic profile. Methods LCR/HCR rats were randomized to high intensity low volume interval treadmill training twice a week or sedentary control for 3 or 11 months before they were sacrificed, at 9 and 18 months of age, respectively. Magnetic resonance spectra were acquired from soleus muscle extracts, and partial least square discriminative analysis was used to determine the differences in metabolic profile. Results Sedentary HCR rats had 54% and 30% higher VO2max compared to sedentary LCR rats at 9 months and 18 months, respectively. In HCR, exercise increased running speed significantly, and VO2max was higher at age of 9 months, compared to sedentary counterparts. In LCR, changes were small and did not reach the level of significance. The metabolic profile was significantly different in the LCR sedentary group compared to the HCR sedentary group at the age of 9 and 18 months, with higher glutamine and glutamate levels (9 months) and lower lactate level (18 months) in HCR. Irrespective of fitness level, aging was associated with increased soleus muscle concentrations of glycerophosphocholine and glucose. Interval training did not influence metabolic profiles in LCR or HCR rats at any age. Conclusion Differences in inborn aerobic capacity gave the most marked contrasts in metabolic profile, there were also some changes with ageing. Low volume high intensity interval training twice a week had no detectable effect on metabolic profile. Copyright: © 2018 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::05e5a4cf0d24695e17802012c8ed747dTest
https://pubmed.ncbi.nlm.nih.gov/30533031Test

المؤلفون: Gianluigi Condorelli, Federica Riva, Roberto Papait, Tomas Stølen, Elisa Di Pasquale, Debora Vignali, Marinos Kallikourdis, Daniele Catalucci, Claudia Sardi, Leonardo Elia, Giuliana Roselli, Anne Marie Ormbostad Berre, Giuseppe Faggian, Pierluigi Carullo, Andrea Fumero, Carolina M. Greco, Elisa Martini, Cristiano Rumio

المصدر: Web of Science
Nature Communications
Nature Communications, Vol 8, Iss 1, Pp 1-14 (2017)

مصطلحات موضوعية: Male, 0301 basic medicine, Genetics and Molecular Biology (all), TCell, T-Lymphocytes, medicine.medical_treatment, General Physics and Astronomy, heart failure, 030204 cardiovascular system & hematology, Biochemistry, 0302 clinical medicine, FOLLICULAR HELPER, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Cells, Cultured, IN-VIVO, Mice, Knockout, Multidisciplinary, Chemistry (all), MURINE MODEL, Interleukin-10, 3. Good health, Interleukin 10, Cytokine, costimulation, Rheumatoid arthritis, SYSTEMIC-LUPUS-ERYTHEMATOSUS, MYOCARDIAL-INFARCTION, MURINE MODEL, DILATED CARDIOMYOPATHY, RHEUMATOID-ARTHRITIS, FOLLICULAR HELPER, SELF-TOLERANCE, FAILING HEART, STEADY-STATE, IN-VIVO, medicine.symptom, Immunosuppressive Agents, medicine.drug, musculoskeletal diseases, STEADY-STATE, Science, TCell, costimulation, heart failure, Cardiomegaly, Inflammation, Article, General Biochemistry, Genetics and Molecular Biology, Abatacept, SELF-TOLERANCE, 03 medical and health sciences, Physics and Astronomy (all), Pressure, medicine, Animals, Humans, FAILING HEART, Pressure overload, business.industry, Macrophages, General Chemistry, medicine.disease, DILATED CARDIOMYOPATHY, Blockade, RHEUMATOID-ARTHRITIS, Mice, Inbred C57BL, 030104 developmental biology, Animals, Newborn, MYOCARDIAL-INFARCTION, Heart failure, Immunology, Cancer research, Biochemistry, Genetics and Molecular Biology (all), business

الوصف: Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients. T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept, leads to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurs via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Abatacept treatment also induces production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice are refractive to treatment, while protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade might be therapeutically exploited to treat HF.
Abatacept is an FDA-approved drug used for treatment of rheumatoid arthritis. Here the authors show that abatacept reduces cardiomyocyte death in a mouse model of heart failure by inhibiting activation and heart infiltration of T cells and macrophages, an effect mediated by IL-10, suggesting a potential therapy for heart failure.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f386111f783e04812013dc8f91b2ebc4Test
http://hdl.handle.net/11562/971509Test