Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart Failure
Aim: Dysfunction of the cardiac ryanodine receptor (RyR2) is an almost ubiquitous finding in animal models of heart failure (HF) and results in abnormal Ca2+ release in cardiomyocytes that contributes to contractile impairment and arrhythmias. We tested whether exercise training (ET), as recommended...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2020.623922/full |
| _version_ | 1819049944067080192 |
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| author | Tore Kristian Danielsen Tore Kristian Danielsen Mani Sadredini Mani Sadredini Ravinea Manotheepan Ravinea Manotheepan Jan Magnus Aronsen Jan Magnus Aronsen Michael Frisk Michael Frisk Marie Haugsten Hansen Marie Haugsten Hansen Kjetil Wessel Andressen Karina Hougen Finn Olav Levy William E. Louch William E. Louch Ole Mathias Sejersted Ole Mathias Sejersted Ivar Sjaastad Ivar Sjaastad Mathis Korseberg Stokke Mathis Korseberg Stokke |
| author_facet | Tore Kristian Danielsen Tore Kristian Danielsen Mani Sadredini Mani Sadredini Ravinea Manotheepan Ravinea Manotheepan Jan Magnus Aronsen Jan Magnus Aronsen Michael Frisk Michael Frisk Marie Haugsten Hansen Marie Haugsten Hansen Kjetil Wessel Andressen Karina Hougen Finn Olav Levy William E. Louch William E. Louch Ole Mathias Sejersted Ole Mathias Sejersted Ivar Sjaastad Ivar Sjaastad Mathis Korseberg Stokke Mathis Korseberg Stokke |
| author_sort | Tore Kristian Danielsen |
| collection | DOAJ |
| description | Aim: Dysfunction of the cardiac ryanodine receptor (RyR2) is an almost ubiquitous finding in animal models of heart failure (HF) and results in abnormal Ca2+ release in cardiomyocytes that contributes to contractile impairment and arrhythmias. We tested whether exercise training (ET), as recommended by current guidelines, had the potential to stabilize RyR2-dependent Ca2+ release in rats with post-myocardial infarction HF.Materials and Methods: We subjected male Wistar rats to left coronary artery ligation or sham operations. After 1 week, animals were characterized by echocardiography and randomized to high-intensity interval ET on treadmills or to sedentary behavior (SED). Running speed was adjusted based on a weekly VO2max test. We repeated echocardiography after 5 weeks of ET and harvested left ventricular cardiomyocytes for analysis of RyR2-dependent systolic and spontaneous Ca2+ release. Phosphoproteins were analyzed by Western blotting, and beta-adrenoceptor density was quantified by radioligand binding.Results: ET increased VO2max in HF-ET rats to 127% of HF-SED (P < 0.05). This coincided with attenuated spontaneous SR Ca2+ release in left ventricular cardiomyocytes from HF-ET but also reduced Ca2+ transient amplitude and slowed Ca2+ reuptake during adrenoceptor activation. However, ventricular diameter and fractional shortening were unaffected by ET. Analysis of Ca2+ homeostasis and major proteins involved in the regulation of SR Ca2+ release and reuptake could not explain the attenuated spontaneous SR Ca2+ release or reduced Ca2+ transient amplitude. Importantly, measurements of beta-adrenoceptors showed a normalization of beta1-adrenoceptor density and beta1:beta2-adrenoceptor ratio in HF-ET.Conclusion: ET increased aerobic capacity in post-myocardial infarction HF rats and stabilized RyR2-dependent Ca2+ release. Our data show that these effects of ET can be gained without major alterations in SR Ca2+ regulatory proteins and indicate that future studies should include upstream parts of the sympathetic signaling pathway. |
| first_indexed | 2024-12-21T11:40:11Z |
| format | Article |
| id | doaj.art-742b0c47400d485daecd637b659300cd |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-21T11:40:11Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-742b0c47400d485daecd637b659300cd2022-12-21T19:05:19ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-01-01710.3389/fcvm.2020.623922623922Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart FailureTore Kristian Danielsen0Tore Kristian Danielsen1Mani Sadredini2Mani Sadredini3Ravinea Manotheepan4Ravinea Manotheepan5Jan Magnus Aronsen6Jan Magnus Aronsen7Michael Frisk8Michael Frisk9Marie Haugsten Hansen10Marie Haugsten Hansen11Kjetil Wessel Andressen12Karina Hougen13Finn Olav Levy14William E. Louch15William E. Louch16Ole Mathias Sejersted17Ole Mathias Sejersted18Ivar Sjaastad19Ivar Sjaastad20Mathis Korseberg Stokke21Mathis Korseberg Stokke22Institute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayKristian Gerhard (KG) Jebsen Centre for Cardiac Research, University of Oslo, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayKristian Gerhard (KG) Jebsen Centre for Cardiac Research, University of Oslo, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayKristian Gerhard (KG) Jebsen Centre for Cardiac Research, University of Oslo, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayBjørknes College, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayKristian Gerhard (KG) Jebsen Centre for Cardiac Research, University of Oslo, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayKristian Gerhard (KG) Jebsen Centre for Cardiac Research, University of Oslo, Oslo, NorwayDepartment of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayDepartment of Pharmacology, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayKristian Gerhard (KG) Jebsen Centre for Cardiac Research, University of Oslo, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayKristian Gerhard (KG) Jebsen Centre for Cardiac Research, University of Oslo, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayKristian Gerhard (KG) Jebsen Centre for Cardiac Research, University of Oslo, Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, NorwayKristian Gerhard (KG) Jebsen Centre for Cardiac Research, University of Oslo, Oslo, NorwayAim: Dysfunction of the cardiac ryanodine receptor (RyR2) is an almost ubiquitous finding in animal models of heart failure (HF) and results in abnormal Ca2+ release in cardiomyocytes that contributes to contractile impairment and arrhythmias. We tested whether exercise training (ET), as recommended by current guidelines, had the potential to stabilize RyR2-dependent Ca2+ release in rats with post-myocardial infarction HF.Materials and Methods: We subjected male Wistar rats to left coronary artery ligation or sham operations. After 1 week, animals were characterized by echocardiography and randomized to high-intensity interval ET on treadmills or to sedentary behavior (SED). Running speed was adjusted based on a weekly VO2max test. We repeated echocardiography after 5 weeks of ET and harvested left ventricular cardiomyocytes for analysis of RyR2-dependent systolic and spontaneous Ca2+ release. Phosphoproteins were analyzed by Western blotting, and beta-adrenoceptor density was quantified by radioligand binding.Results: ET increased VO2max in HF-ET rats to 127% of HF-SED (P < 0.05). This coincided with attenuated spontaneous SR Ca2+ release in left ventricular cardiomyocytes from HF-ET but also reduced Ca2+ transient amplitude and slowed Ca2+ reuptake during adrenoceptor activation. However, ventricular diameter and fractional shortening were unaffected by ET. Analysis of Ca2+ homeostasis and major proteins involved in the regulation of SR Ca2+ release and reuptake could not explain the attenuated spontaneous SR Ca2+ release or reduced Ca2+ transient amplitude. Importantly, measurements of beta-adrenoceptors showed a normalization of beta1-adrenoceptor density and beta1:beta2-adrenoceptor ratio in HF-ET.Conclusion: ET increased aerobic capacity in post-myocardial infarction HF rats and stabilized RyR2-dependent Ca2+ release. Our data show that these effects of ET can be gained without major alterations in SR Ca2+ regulatory proteins and indicate that future studies should include upstream parts of the sympathetic signaling pathway.https://www.frontiersin.org/articles/10.3389/fcvm.2020.623922/fullexercise trainingarrhythmiascardiac ryanodine receptorheart failuremyocardial infarction |
| spellingShingle | Tore Kristian Danielsen Tore Kristian Danielsen Mani Sadredini Mani Sadredini Ravinea Manotheepan Ravinea Manotheepan Jan Magnus Aronsen Jan Magnus Aronsen Michael Frisk Michael Frisk Marie Haugsten Hansen Marie Haugsten Hansen Kjetil Wessel Andressen Karina Hougen Finn Olav Levy William E. Louch William E. Louch Ole Mathias Sejersted Ole Mathias Sejersted Ivar Sjaastad Ivar Sjaastad Mathis Korseberg Stokke Mathis Korseberg Stokke Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart Failure Frontiers in Cardiovascular Medicine exercise training arrhythmias cardiac ryanodine receptor heart failure myocardial infarction |
| title | Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart Failure |
| title_full | Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart Failure |
| title_fullStr | Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart Failure |
| title_full_unstemmed | Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart Failure |
| title_short | Exercise Training Stabilizes RyR2-Dependent Ca2+ Release in Post-infarction Heart Failure |
| title_sort | exercise training stabilizes ryr2 dependent ca2 release in post infarction heart failure |
| topic | exercise training arrhythmias cardiac ryanodine receptor heart failure myocardial infarction |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2020.623922/full |
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