Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction
Arrhythmias are a hallmark of myocardial infarction (MI) and increase patient mortality. How insult to the cardiac conduction system causes arrhythmias following MI is poorly understood. Here, we demonstrate conduction system restoration during neonatal mouse heart regeneration versus pathological r...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature [academic journals on nature.com]
2025
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| _version_ | 1824459304585920512 |
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| author | Sayers, JR Martinez-Navarro, H Sun, X de Villiers, C Sigal, S Weinberger, M Rodriguez, CC Riebel, LL Berg, LA Camps, J Herring, N Rodriguez, B Sauka-Spengler, T Riley, PR |
| author_facet | Sayers, JR Martinez-Navarro, H Sun, X de Villiers, C Sigal, S Weinberger, M Rodriguez, CC Riebel, LL Berg, LA Camps, J Herring, N Rodriguez, B Sauka-Spengler, T Riley, PR |
| author_sort | Sayers, JR |
| collection | OXFORD |
| description | Arrhythmias are a hallmark of myocardial infarction (MI) and increase patient mortality. How insult to the cardiac conduction system causes arrhythmias following MI is poorly understood. Here, we demonstrate conduction system restoration during neonatal mouse heart regeneration versus pathological remodeling at non-regenerative stages. Tissue-cleared whole-organ imaging identified disorganized bundling of conduction fibers after MI and global His–Purkinje disruption. Single-cell RNA sequencing (scRNA-seq) revealed specific molecular changes to regenerate the conduction network versus aberrant electrical alterations during fibrotic repair. This manifested functionally as a transition from normal rhythm to pathological conduction delay beyond the regenerative window. Modeling in the infarcted human heart implicated the non-regenerative phenotype as causative for heart block, as observed in patients. These findings elucidate the mechanisms underpinning conduction system regeneration and reveal how MI-induced damage elicits clinical arrhythmogenesis. |
| first_indexed | 2025-02-19T04:39:40Z |
| format | Journal article |
| id | oxford-uuid:7a74b808-2994-4492-9065-5cc6bb652590 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-02-19T04:39:40Z |
| publishDate | 2025 |
| publisher | Springer Nature [academic journals on nature.com] |
| record_format | dspace |
| spelling | oxford-uuid:7a74b808-2994-4492-9065-5cc6bb6525902025-02-14T20:19:01ZCardiac conduction system regeneration prevents arrhythmias after myocardial infarctionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7a74b808-2994-4492-9065-5cc6bb652590EnglishJisc Publications RouterSpringer Nature [academic journals on nature.com]2025Sayers, JRMartinez-Navarro, HSun, Xde Villiers, CSigal, SWeinberger, MRodriguez, CCRiebel, LLBerg, LACamps, JHerring, NRodriguez, BSauka-Spengler, TRiley, PRArrhythmias are a hallmark of myocardial infarction (MI) and increase patient mortality. How insult to the cardiac conduction system causes arrhythmias following MI is poorly understood. Here, we demonstrate conduction system restoration during neonatal mouse heart regeneration versus pathological remodeling at non-regenerative stages. Tissue-cleared whole-organ imaging identified disorganized bundling of conduction fibers after MI and global His–Purkinje disruption. Single-cell RNA sequencing (scRNA-seq) revealed specific molecular changes to regenerate the conduction network versus aberrant electrical alterations during fibrotic repair. This manifested functionally as a transition from normal rhythm to pathological conduction delay beyond the regenerative window. Modeling in the infarcted human heart implicated the non-regenerative phenotype as causative for heart block, as observed in patients. These findings elucidate the mechanisms underpinning conduction system regeneration and reveal how MI-induced damage elicits clinical arrhythmogenesis. |
| spellingShingle | Sayers, JR Martinez-Navarro, H Sun, X de Villiers, C Sigal, S Weinberger, M Rodriguez, CC Riebel, LL Berg, LA Camps, J Herring, N Rodriguez, B Sauka-Spengler, T Riley, PR Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction |
| title | Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction |
| title_full | Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction |
| title_fullStr | Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction |
| title_full_unstemmed | Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction |
| title_short | Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction |
| title_sort | cardiac conduction system regeneration prevents arrhythmias after myocardial infarction |
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