Related Experiment Video
Updated: Sep 28, 2025
Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications
Published on: May 18, 2017
Determination of Agrin and Related Proteins Levels as a Function of Age in Human Hearts
Katie L Skeffington1, Ffion P Jones1, M Saadeh Suleiman1
1Bristol Heart Institute, Research Floor Level 7, Bristol Royal Infirmary, Bristol, United Kingdom.
Insights
Agrin, a protein crucial for heart development, decreases with age in human hearts. This finding suggests potential for agrin-based therapies to repair cardiac injury, similar to rodent models.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Molecular Cardiology
Background:
- Mature cardiomyocytes (heart muscle cells) cannot divide, hindering adult heart repair after injury.
- Rodent studies indicate the extracellular matrix protein agrin promotes cardiomyocyte proliferation during development.
- Agrin expression declines after birth, coinciding with the cessation of cardiomyocyte proliferation.
Purpose of the Study:
- To investigate the presence and expression of agrin in human heart tissue.
- To determine if agrin expression changes with age in the human heart.
- To compare human agrin expression patterns with those observed in rodent models.
Main Methods:
- Right ventricular (RV) biopsies were obtained from 40 patients undergoing congenital heart disease surgery.
- Agrin and associated protein expression was analyzed using transcript analysis, immunohistochemistry, and western blots.
- Patient data was analyzed for correlations between protein levels, age, gender, and pathology.
Main Results:
- Agrin and laminin transcripts were detected in all human RV samples.
- Agrin and laminin transcript levels showed a significant negative correlation with patient age.
- Protein presence was confirmed across all age groups, with agrin showing age-dependent downregulation, albeit less pronounced than in mice.
Conclusions:
- Agrin expression is progressively downregulated with age in human right ventricular tissue.
- Human findings show similarities and differences compared to rodent models of agrin expression.
- These results support further research into agrin-based therapies for human cardiac repair.
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.
