Abstract
Cardiac valve structure and function are complex and include dynamic interactions between cells, extracellular matrix (ECM) and their hemodynamic environment. Valvular gene expression is tightly regulated by a variety of mechanisms including epigenetic factors such as histone modifications, RNA-based mechanisms and DNA methylation. To date, methylation fingerprints of non-diseased human aortic and mitral valves have not been studied. In this work I analyzed the differential methylation profiles of 12 non-diseased aortic and mitral valve tissue samples (in matched pairs). Methylation data were acquired via reduced representation bisulfite sequencing (RRBS). Of 1601 promoters analyzed genome-wide, my analysis revealed 584 differentially methylated (DM) promoters, of which 13 were reported in endothelial mesenchymal trans-differentiation (EMT), 37 in aortic and mitral valve disease and 7 in ECM remodeling. Both functional classification and network analysis showed that genes associated with the differentially methylated promoters were enriched for WNT-, Cadherin-, Endothelin-, PDGF- and VEGF- signaling implicated in valvular physiology and pathophysiology. Additional enrichment was detected for TGFB-, NOTCH- and Integrin- signaling involved in EMT as well as ECM remodeling. These data provide the first insight into differential regulation of human aortic and mitral valve tissue and identify candidate genes linked to differentially methylated promoters. This work will improve the understanding of valve biology, valve tissue engineering approaches and contributes to the identification of relevant drug targets.
Department
Biotechnology Program
Degree Name
PhD in Applied Science
Graduation Date
Fall 12-9-2020
Submission Date
1-25-2021
First Advisor
Ahmed Moustafa
Second Advisor
Yasmine Aguib
Third Advisor
Magdi Yacoub
Committee Member 1
Elena Aikawa
Committee Member 2
Ramy Aziz
Committee Member 3
Suher Zada and Ahmed Abdellatif
Extent
219 p.
Document Type
Doctoral Dissertation
Institutional Review Board (IRB) Approval
Approval has been obtained for this item
Recommended Citation
APA Citation
Halawa, S.
(2020).Profiling Genome-Wide DNA Methylation Patterns in Human Aortic and Mitral Valves [Doctoral Dissertation, the American University in Cairo]. AUC Knowledge Fountain.
https://fount.aucegypt.edu/etds/1519
MLA Citation
Halawa, Sarah. Profiling Genome-Wide DNA Methylation Patterns in Human Aortic and Mitral Valves. 2020. American University in Cairo, Doctoral Dissertation. AUC Knowledge Fountain.
https://fount.aucegypt.edu/etds/1519