The creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injury
Restoring blood flow following an acute myocardial infarction saves lives, but results in tissue damage due to ischaemia–reperfusion injury (I/R). Ameliorating this damage is a major research goal to improve recovery and reduce subsequent morbidity due to heart failure. Both the ischaemic and reperf...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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Portland Press
2018
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| _version_ | 1826265884359917568 |
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| author | Cao, F Zervou, S Lygate, C |
| author_facet | Cao, F Zervou, S Lygate, C |
| author_sort | Cao, F |
| collection | OXFORD |
| description | Restoring blood flow following an acute myocardial infarction saves lives, but results in tissue damage due to ischaemia–reperfusion injury (I/R). Ameliorating this damage is a major research goal to improve recovery and reduce subsequent morbidity due to heart failure. Both the ischaemic and reperfusion phases represent crises of cellular energy provision in which the mitochondria play a central role. This mini-review will explore the rationale and therapeutic potential of augmenting the creatine kinase (CK) energy shuttle, which constitutes the primary short-term energy buffer and transport system in the cardiomyocyte. Proof-of-principle data from several transgenic mouse models have demonstrated robust cardioprotection by either raising myocardial creatine levels or by overexpressing specific CK isoforms. The effect on cardiac function, high-energy phosphates and myocardial injury will be discussed and possible directions for future research highlighted. We conclude that the CK system represents a viable target for therapeutic intervention in I/R injury; however, much needed translational studies will require the development of new pharmacological tools. |
| first_indexed | 2024-03-06T20:30:36Z |
| format | Journal article |
| id | oxford-uuid:30e6642c-1e11-4124-8acd-ab0109d10953 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:30:36Z |
| publishDate | 2018 |
| publisher | Portland Press |
| record_format | dspace |
| spelling | oxford-uuid:30e6642c-1e11-4124-8acd-ab0109d109532022-03-26T13:04:30ZThe creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injuryJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:30e6642c-1e11-4124-8acd-ab0109d10953EnglishSymplectic Elements at OxfordPortland Press2018Cao, FZervou, SLygate, CRestoring blood flow following an acute myocardial infarction saves lives, but results in tissue damage due to ischaemia–reperfusion injury (I/R). Ameliorating this damage is a major research goal to improve recovery and reduce subsequent morbidity due to heart failure. Both the ischaemic and reperfusion phases represent crises of cellular energy provision in which the mitochondria play a central role. This mini-review will explore the rationale and therapeutic potential of augmenting the creatine kinase (CK) energy shuttle, which constitutes the primary short-term energy buffer and transport system in the cardiomyocyte. Proof-of-principle data from several transgenic mouse models have demonstrated robust cardioprotection by either raising myocardial creatine levels or by overexpressing specific CK isoforms. The effect on cardiac function, high-energy phosphates and myocardial injury will be discussed and possible directions for future research highlighted. We conclude that the CK system represents a viable target for therapeutic intervention in I/R injury; however, much needed translational studies will require the development of new pharmacological tools. |
| spellingShingle | Cao, F Zervou, S Lygate, C The creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injury |
| title | The creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injury |
| title_full | The creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injury |
| title_fullStr | The creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injury |
| title_full_unstemmed | The creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injury |
| title_short | The creatine kinase system as a therapeutic target for myocardial ischaemia-reperfusion injury |
| title_sort | creatine kinase system as a therapeutic target for myocardial ischaemia reperfusion injury |
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