Salman, Wesam (2025) Understanding how exercise and standard-of-care drugs affect iPSC-derived cardiomyocytes from a male ACM patient. Masters thesis, Memorial University of Newfoundland.
Full text not available from this repository.
Abstract
Arrhythmogenic Cardiomyopathy (ACM) is a heart disease causing sudden cardiac death and heart failure. There is a large population of ACM patients in Newfoundland and Labrador (NL) with an autosomal dominant mutation in the TMEM43 gene (TMEM43-S358L). The Esseltine lab collected dermal punch biopsies from several NL ACM patients harbouring the TMEM43 mutation and genetically reprogrammed these skin cells into induced pluripotent stem cells (iPSCs). Additionally, we sought to investigate the fibrosis component of the disease using ACM patient dermal fibroblasts. However, IPSCs can differentiate into any cell type in the body, including cardiomyocytes. The two largest factors for severe disease presentation include being male and engaging in exercise. Although it is unknown how exercise exacerbates arrhythmogenicity in ACM, it is postulated to occur through adrenaline stimulation of the β-adrenergic receptor. In fact, β-blockers are standard-of-care treatment for ACM patients. Therefore, we are investigating how male ACM patient-derived iPSC-cardiomyocytes respond to the β-adrenergic receptor modulation. Unstimulated male ACM iPSC-cardiomyocytes demonstrate disturbed contraction frequencies and aberrations in calcium handling compared to unaffected male control iPSC-cardiomyocytes. β-adrenergic modulation did not affect the frequency of contraction for ACM patient iPSC-CMs. Dermal fibroblasts experiments showed fibrotic features for the ACM patient fibroblasts. Future studies will identify personalized treatment strategies for ACM patients, and how the TMEM43-S358L mutation leads to cardiac fibrosis.
| Item Type: | Thesis (Masters) |
|---|---|
| URI: | http://research.library.mun.ca/id/eprint/16936 |
| Item ID: | 16936 |
| Additional Information: | Includes bibliographical references (pages 82-97) -- Restricted until March 21, 2026 |
| Keywords: | ACM, cardiomyocytes, iPSC, heart disease |
| Department(s): | Medicine, Faculty of > Biomedical Sciences |
| Date: | May 2025 |
| Date Type: | Submission |
| Medical Subject Heading: | Arrhythmias, Cardiac; Heart Diseases; Cardiomyopathies; Adrenergic Agents; Newfoundland and Labrador |
Actions (login required)
 |
View Item |
