Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies
Inherited cardiomyopathies caused by pathological genetic variants include multiple subtypes of heart disease. Advances in next-generation sequencing (NGS) techniques have allowed for the identification of numerous genetic variants as pathological variants. However, the disease penetrance varies amo...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1114459/full |
| _version_ | 1797943294823497728 |
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| author | Karen R. Gaar-Humphreys Karen R. Gaar-Humphreys Alyssa van den Brink Alyssa van den Brink Mark Wekking Mark Wekking Folkert W. Asselbergs Folkert W. Asselbergs Frank G. van Steenbeek Frank G. van Steenbeek Frank G. van Steenbeek Magdalena Harakalova Magdalena Harakalova Magdalena Harakalova Jiayi Pei Jiayi Pei Jiayi Pei |
| author_facet | Karen R. Gaar-Humphreys Karen R. Gaar-Humphreys Alyssa van den Brink Alyssa van den Brink Mark Wekking Mark Wekking Folkert W. Asselbergs Folkert W. Asselbergs Frank G. van Steenbeek Frank G. van Steenbeek Frank G. van Steenbeek Magdalena Harakalova Magdalena Harakalova Magdalena Harakalova Jiayi Pei Jiayi Pei Jiayi Pei |
| author_sort | Karen R. Gaar-Humphreys |
| collection | DOAJ |
| description | Inherited cardiomyopathies caused by pathological genetic variants include multiple subtypes of heart disease. Advances in next-generation sequencing (NGS) techniques have allowed for the identification of numerous genetic variants as pathological variants. However, the disease penetrance varies among mutated genes. Some can be associated with more than one disease subtype, leading to a complex genotype-phenotype relationship in inherited cardiomyopathies. Previous studies have demonstrated disrupted metabolism in inherited cardiomyopathies and the importance of metabolic adaptations in disease onset and progression. In addition, genotype- and phenotype-specific metabolic alterations, especially in lipid metabolism, have been revealed. In this mini-review, we describe the metabolic changes that are associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), which account for the largest proportion of inherited cardiomyopathies. We also summarize the affected expression of genes involved in fatty acid oxidation (FAO) in DCM and HCM, highlighting the potential of PPARA-targeting drugs as FAO modulators in treating patients with inherited cardiomyopathies. |
| first_indexed | 2024-04-10T20:21:54Z |
| format | Article |
| id | doaj.art-46f07cef590b4d50b2ef9234bac68380 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-10T20:21:54Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-46f07cef590b4d50b2ef9234bac683802023-01-25T16:29:13ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-01-011010.3389/fcvm.2023.11144591114459Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathiesKaren R. Gaar-Humphreys0Karen R. Gaar-Humphreys1Alyssa van den Brink2Alyssa van den Brink3Mark Wekking4Mark Wekking5Folkert W. Asselbergs6Folkert W. Asselbergs7Frank G. van Steenbeek8Frank G. van Steenbeek9Frank G. van Steenbeek10Magdalena Harakalova11Magdalena Harakalova12Magdalena Harakalova13Jiayi Pei14Jiayi Pei15Jiayi Pei16Division Heart and Lungs, Department of Cardiology, Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, NetherlandsDivision Heart and Lungs, Department of Cardiology, Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, NetherlandsDivision Heart and Lungs, Department of Cardiology, Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Cardiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsHealth Data Research United Kingdom and Institute of Health Informatics, University College London, London, United KingdomDivision Heart and Lungs, Department of Cardiology, Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDivision Heart and Lungs, Department of Cardiology, Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, NetherlandsNetherlands Heart Institute, Utrecht, NetherlandsDivision Heart and Lungs, Department of Cardiology, Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University, Utrecht, NetherlandsRegenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, NetherlandsNetherlands Heart Institute, Utrecht, NetherlandsInherited cardiomyopathies caused by pathological genetic variants include multiple subtypes of heart disease. Advances in next-generation sequencing (NGS) techniques have allowed for the identification of numerous genetic variants as pathological variants. However, the disease penetrance varies among mutated genes. Some can be associated with more than one disease subtype, leading to a complex genotype-phenotype relationship in inherited cardiomyopathies. Previous studies have demonstrated disrupted metabolism in inherited cardiomyopathies and the importance of metabolic adaptations in disease onset and progression. In addition, genotype- and phenotype-specific metabolic alterations, especially in lipid metabolism, have been revealed. In this mini-review, we describe the metabolic changes that are associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), which account for the largest proportion of inherited cardiomyopathies. We also summarize the affected expression of genes involved in fatty acid oxidation (FAO) in DCM and HCM, highlighting the potential of PPARA-targeting drugs as FAO modulators in treating patients with inherited cardiomyopathies.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1114459/fullhypertrophic cardiomyopathydilated cardiomyopathygenetic variantslipid metabolismfatty acid oxidationtranscription factor PPARA |
| spellingShingle | Karen R. Gaar-Humphreys Karen R. Gaar-Humphreys Alyssa van den Brink Alyssa van den Brink Mark Wekking Mark Wekking Folkert W. Asselbergs Folkert W. Asselbergs Frank G. van Steenbeek Frank G. van Steenbeek Frank G. van Steenbeek Magdalena Harakalova Magdalena Harakalova Magdalena Harakalova Jiayi Pei Jiayi Pei Jiayi Pei Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies Frontiers in Cardiovascular Medicine hypertrophic cardiomyopathy dilated cardiomyopathy genetic variants lipid metabolism fatty acid oxidation transcription factor PPARA |
| title | Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies |
| title_full | Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies |
| title_fullStr | Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies |
| title_full_unstemmed | Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies |
| title_short | Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies |
| title_sort | targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies |
| topic | hypertrophic cardiomyopathy dilated cardiomyopathy genetic variants lipid metabolism fatty acid oxidation transcription factor PPARA |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1114459/full |
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