Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In Vitro
(1) Background: The exact mechanism(s) underlying pathological changes in a heart in transition to hypertrophy and failure are not yet fully understood. However, alterations in cardiac energy metabolism seem to be an important contributor. We characterized an in vitro model of adrenergic stimulation...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/7/3620 |
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| author | Ilvy M. E. Geraets Will A. Coumans Agnieszka Strzelecka Patrick Schönleitner Gudrun Antoons Francesco Schianchi Myrthe M. A. Willemars Dimitrios Kapsokalyvas Jan F. C. Glatz Joost J. F. P. Luiken Miranda Nabben |
| author_facet | Ilvy M. E. Geraets Will A. Coumans Agnieszka Strzelecka Patrick Schönleitner Gudrun Antoons Francesco Schianchi Myrthe M. A. Willemars Dimitrios Kapsokalyvas Jan F. C. Glatz Joost J. F. P. Luiken Miranda Nabben |
| author_sort | Ilvy M. E. Geraets |
| collection | DOAJ |
| description | (1) Background: The exact mechanism(s) underlying pathological changes in a heart in transition to hypertrophy and failure are not yet fully understood. However, alterations in cardiac energy metabolism seem to be an important contributor. We characterized an in vitro model of adrenergic stimulation-induced cardiac hypertrophy for studying metabolic, structural, and functional changes over time. Accordingly, we investigated whether metabolic interventions prevent cardiac structural and functional changes; (2) Methods: Primary rat cardiomyocytes were treated with phenylephrine (PE) for 16 h, 24 h, or 48 h, whereafter hypertrophic marker expression, protein synthesis rate, glucose uptake, and contractile function were assessed; (3) Results: 24 h PE treatment increased expression of hypertrophic markers, phosphorylation of hypertrophy-related signaling kinases, protein synthesis, and glucose uptake. Importantly, the increased glucose uptake preceded structural and functional changes, suggesting a causal role for metabolism in the onset of PE-induced hypertrophy. Indeed, PE treatment in the presence of a PAN-Akt inhibitor or of a GLUT4 inhibitor dipyridamole prevented PE-induced increases in cellular glucose uptake and ameliorated PE-induced contractile alterations; (4) Conclusions: Pharmacological interventions, forcing substrate metabolism away from glucose utilization, improved contractile properties in PE-treated cardiomyocytes, suggesting that targeting glucose uptake, independent from protein synthesis, forms a promising strategy to prevent hypertrophy and hypertrophy-induced cardiac dysfunction. |
| first_indexed | 2024-03-10T12:45:58Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:45:58Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dc228c9f9206495a8e1bb0573d0e016c2023-11-21T13:32:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01227362010.3390/ijms22073620Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In VitroIlvy M. E. Geraets0Will A. Coumans1Agnieszka Strzelecka2Patrick Schönleitner3Gudrun Antoons4Francesco Schianchi5Myrthe M. A. Willemars6Dimitrios Kapsokalyvas7Jan F. C. Glatz8Joost J. F. P. Luiken9Miranda Nabben10Department of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartment of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartment of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartments of Physiology, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartments of Physiology, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartment of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartment of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartment of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartment of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartment of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200-MD Maastricht, The NetherlandsDepartment of Genetics & Cell Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6200-MD Maastricht, The Netherlands(1) Background: The exact mechanism(s) underlying pathological changes in a heart in transition to hypertrophy and failure are not yet fully understood. However, alterations in cardiac energy metabolism seem to be an important contributor. We characterized an in vitro model of adrenergic stimulation-induced cardiac hypertrophy for studying metabolic, structural, and functional changes over time. Accordingly, we investigated whether metabolic interventions prevent cardiac structural and functional changes; (2) Methods: Primary rat cardiomyocytes were treated with phenylephrine (PE) for 16 h, 24 h, or 48 h, whereafter hypertrophic marker expression, protein synthesis rate, glucose uptake, and contractile function were assessed; (3) Results: 24 h PE treatment increased expression of hypertrophic markers, phosphorylation of hypertrophy-related signaling kinases, protein synthesis, and glucose uptake. Importantly, the increased glucose uptake preceded structural and functional changes, suggesting a causal role for metabolism in the onset of PE-induced hypertrophy. Indeed, PE treatment in the presence of a PAN-Akt inhibitor or of a GLUT4 inhibitor dipyridamole prevented PE-induced increases in cellular glucose uptake and ameliorated PE-induced contractile alterations; (4) Conclusions: Pharmacological interventions, forcing substrate metabolism away from glucose utilization, improved contractile properties in PE-treated cardiomyocytes, suggesting that targeting glucose uptake, independent from protein synthesis, forms a promising strategy to prevent hypertrophy and hypertrophy-induced cardiac dysfunction.https://www.mdpi.com/1422-0067/22/7/3620cardiac hypertrophyglucose uptakephenylephrinemetabolic modulationadult rat cardiomyocytes |
| spellingShingle | Ilvy M. E. Geraets Will A. Coumans Agnieszka Strzelecka Patrick Schönleitner Gudrun Antoons Francesco Schianchi Myrthe M. A. Willemars Dimitrios Kapsokalyvas Jan F. C. Glatz Joost J. F. P. Luiken Miranda Nabben Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In Vitro International Journal of Molecular Sciences cardiac hypertrophy glucose uptake phenylephrine metabolic modulation adult rat cardiomyocytes |
| title | Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In Vitro |
| title_full | Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In Vitro |
| title_fullStr | Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In Vitro |
| title_full_unstemmed | Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In Vitro |
| title_short | Metabolic Interventions to Prevent Hypertrophy-Induced Alterations in Contractile Properties In Vitro |
| title_sort | metabolic interventions to prevent hypertrophy induced alterations in contractile properties in vitro |
| topic | cardiac hypertrophy glucose uptake phenylephrine metabolic modulation adult rat cardiomyocytes |
| url | https://www.mdpi.com/1422-0067/22/7/3620 |
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