Deciphering the heterogeneity and functional role of the cardiac stroma in health and disease
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Tung, Lin Wei (Henry)
issued: 2025-03-31T07:00:00Z
issued: 2024
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Heart failure is, in general, an inevitable outcome of ischemic heart disease and various cardiomyopathies. While this is largely attributed to the negligible regenerative capacity of the heart, the deterioration of cardiac function is driven by a myriad of dysregulated processes that culminate in chronic remodeling of the heart. In particular, the cardiac stroma, composed of interstitial mesenchymal cells, represents an important component of the cardiac niche and structure. It acts as a “double-edged” entity that plays a vital role in tissue repair and recovery of cardiac function, yet its involvement in driving pathological alterations leading to complete heart failure cannot be excluded. Thus, understanding the cardiac stroma and identifying mechanisms to alter its behaviour hold significant therapeutic potential. Here, we found that the cardiac stroma is a highly heterogeneous population consisted of multiple anatomically and functionally distinct entities. In response to acute ischemic injury, a subset of perivascular stromal cells known as pericytes acquire a transient signature indicative of increased fibrogenic activity and altered vascular maintenance, which is correlated with their dissociation from the vasculature and the ensuing vascular deterioration in the infarct. This regional response is supported by a niche that perpetuates pro-inflammatory, fibrogenic, and anti-angiogenic signaling beyond the completion of the myocardial scar. Dysregulation of the stroma and its secretome also potentiate the functional deterioration of the cardiac muscle. In chronic contexts such as hypertrophic cardiomyopathy, a subset of fibroblasts adopts an activated state similar to that of acute injuries and upregulates IGF-1 signaling to cardiomyocytes, and therefore inducing a hypertrophic response. Moreover, the abrogation of stromal signals regulating vascular growth and maintenance is indicative of compromised coronary circulation. Collectively, our work underlines the…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/87731
note: Deciphering the heterogeneity and functional role of the cardiac stroma in health and disease by Lin Wei (Henry) Tung B.Sc., Queen’s University, 2019 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2024 © Lin Wei (Henry) Tung, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Deciphering the heterogeneity and functional role of the cardiac stroma in health and disease submitted by Lin Wei (Henry) Tung in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Experimental Medicine Examining Committee: Dr. Fabio M.V. Rossi, Professor, Biomedical Engineering, UBC Supervisor Dr. Kelly M. McNagny, Professor, Biomedical Engineering, UBC Supervisory Committee Member Dr. Zachary Laksman, Professor, Biomedical Engineering, UBC Supervisory Committee Member Dr. Nozomu Yachie, Professor, Biomedical Engineering, UBC University Examiner Dr. Liam Brunham, Associate Professor, Biomedical Engineering, UBC University Examiner Additional Supervisory Committee Members: Dr. Ali Bashashati, Professor, Biomedical Engineering, UBC Supervisory Committee Member iii Abstract Heart failure is, in general, an inevitable outcome of ischemic heart disease and various cardiomyopathies. While this is largely attributed to the negligible regenerative capacity of the heart, the deterioration of cardiac function is driven by a myriad of dysregulated processes that culminate in chronic remodeling of the heart. In particular, the cardiac stroma, composed of interstitial mesenchymal cells, represents an important component of the cardiac niche and structure. It acts as a “double-edged” entity that plays a vital role in tissue repair and recovery of cardiac function, yet its involv…
has type: Thesis/Dissertation
date issued: 2025-05
is shown at: 10.14288/1.0441266
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Rossi, Fabio M. V.
type: Text
identifier URI: http://hdl.handle.net/2429/87731