Abstract
Background: Mature cardiomyocytes are unable to proliferate, preventing the injured adult heart from repairing itself. Studies in rodents have suggested that the extracellular matrix protein agrin promotes cardiomyocyte proliferation in the developing heart and that agrin expression is downregulated shortly after birth, resulting in the cessation of proliferation. Agrin based therapies have proven successful at inducing repair in animal models of cardiac injury, however whether similar pathways exist in the human heart is unknown.
Methods: Right ventricular (RV) biopsies were collected from 40 patients undergoing surgery for congenital heart disease and the expression of agrin and associated proteins was investigated.
Results: Agrin transcripts were found in all samples and their levels were significantly negatively correlated to age (p = 0.026), as were laminin transcripts (p = 0.023), whereas no such correlation was found for the other proteins analyzed. No significant correlations for any of the proteins were found when grouping patients by their gender or pathology. Immunohistochemistry and western blots to detect and localize agrin and the other proteins under analysis in RV tissue, confirmed their presence in patients of all ages.
Conclusions: We show that agrin is progressively downregulated with age in human RV tissue but not as dramatically as has been demonstrated in mice; highlighting both similarities and differences to findings in rodents. Our results lay the groundwork for future studies exploring the potential of agrin-based therapies in the repair of damaged human hearts.
Methods: Right ventricular (RV) biopsies were collected from 40 patients undergoing surgery for congenital heart disease and the expression of agrin and associated proteins was investigated.
Results: Agrin transcripts were found in all samples and their levels were significantly negatively correlated to age (p = 0.026), as were laminin transcripts (p = 0.023), whereas no such correlation was found for the other proteins analyzed. No significant correlations for any of the proteins were found when grouping patients by their gender or pathology. Immunohistochemistry and western blots to detect and localize agrin and the other proteins under analysis in RV tissue, confirmed their presence in patients of all ages.
Conclusions: We show that agrin is progressively downregulated with age in human RV tissue but not as dramatically as has been demonstrated in mice; highlighting both similarities and differences to findings in rodents. Our results lay the groundwork for future studies exploring the potential of agrin-based therapies in the repair of damaged human hearts.
| Original language | English |
|---|---|
| Article number | 813904 |
| Number of pages | 10 |
| Journal | Frontiers in Cardiovascular Medicine |
| Volume | 9 |
| DOIs | |
| Publication status | Published - 9 Mar 2022 |
Bibliographical note
Funding Information:This work was supported by grants from the Sir Jules Thorn Charitable Trust (MC) and the British Heart Foundation, grant no. CH/1/32804 (KS, MB, and MC). FJ is the recipient of a British Heart Foundation PhD studentship in Integrative Cardiovascular Sciences. The Cardiovascular theme of NIHR Bristol Biomedical Research Centre also supported this work. The funders played no role in the design of the study, in the collection, analysis and interpretation of data, or in the decision to submit the manuscript for publication.
Publisher Copyright:
© 2022 Skeffington, Jones, Suleiman, Caputo, Brancaccio and Bigotti.
Keywords
- agrin
- proliferation
- dystroglycan
- extracellular matrix
- myocardial infarction
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Investigating the role of the extracellular matrix protein agrin in cardioprotection: production and characterisation of a bioactive recombinant agrin
Jones, F. P. (Author), Bigotti, G. (Supervisor) & Caputo, M. (Supervisor), 5 Feb 2024Student thesis: Doctoral Thesis › Doctor of Philosophy (PhD)
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