Date of Award

Spring 2023

Degree Type

Thesis

Department

Biological Sciences

Director of Thesis

Dr. Lydia Matesic

First Reader

Dr. Shannon Davis

Second Reader

Dr. Shannon Davis

Abstract

Cardiovascular disease is the leading cause of mortality globally, with the aging population being most vulnerable. Cardiomyocytes and cardiac fibroblasts mediate pathophysiological changes of cardiac aging including interstitial fibrosis, left ventricular hypertrophy, lethal arrhythmias, and eventual culmination in heart failure. Interestingly, subclinical congenital heart disease and hypertrophic cardiomyopathy, originating in embryonic development, induce accelerated cardiac aging. The diverse developmental origins of cardiac fibroblasts suggest that perturbations in gene expression within this heterogeneous cell population during embryonic heart development have significant consequences for cardiac aging. Previous studies implicate the E3 ubiquitin ligase WWP1, a post-translational regulatory protein, in accelerated cardiac aging. Its expression pattern throughout embryonic heart development, however, has not been characterized. This study aimed to characterize the expression of WWP1 throughout a time course of development in the mouse heart. Immunohistochemistry detected broad expression of the WWP1 protein throughout the developing heart, with cytoplasmic localization from E12.5-E15.5 and nuclear localization from E13.5-E15.5 in some cells. Immunofluorescence corroborated these findings and detected WWP1 expression within endocardium-derived, putative cardiac fibroblasts from E12.5-E15.5 timepoints. However, due to the limited number of animals examined and our inability to delineate cell boundaries, additional experimentation is needed to confirm these findings. Nevertheless, given the newly described role for endocardium-derived cardiac fibroblasts in the pathological fibrosis of cardiac aging, further investigation into WWP1 expression during development within this subpopulation of cardiac fibroblasts holds promise in elucidating the consequences of deviations in WWP1 expression for accelerated cardiac aging.

First Page

1

Last Page

49

Rights

© 2023, Savannah L Bowers

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