Advisor(s)
Adam Wende
Farah Lubin
Committee Member(s)
Elizabeth Worthey
Hind Lal
Martin Young
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Microbiology
Date of Award
1-7-2025
Abstract
Cardiovascular disease (CVD) comprises a complex array of disorders affecting the heart and blood vessels, representing the leading cause of mortality worldwide. This multifaceted nature of CVD has prompted extensive research into its molecular underpinnings and etiological diversity. Despite significant advances, the majority of CVD management strategies are guideline-based symptomatic treatment. This necessitates extensive research studies on therapeutic interventions aimed at disease prevention or cure. In this dissertation, we have employed next-generation sequencing (NGS) techniques to elucidate the cardiac transcriptional and epigenetic landscape across various conditions, including ischemic heart failure (IHF), Cardiogenic shock (CS), and diabetic heart failure (DHF). Our objective was to discover molecular signatures that could help us comprehend the underlying mechanisms or serve as potential targets for therapeutic innovation. Through a series of four studies, our findings revealed: 1) distinct transcriptional and DNA methylation patterns in IHF that occur independently of racial disparities, alongside unique alterations specific to African Americans (AAs) and Caucasian Americans (CAs); 2) the identification of microRNA 200b (miRNA-200b) as a prognostic circulating biomarker for CS, as well as its association with mechanical unloading facilitated by percutaneous ventricular assist device (pVAD) support; 3) differentially methylated and expressed genes that may facilitate glycemic memory—a phenomenon wherein prior hyperglycemia predisposes the heart to failure—demonstrated in mouse models exhibiting short-term elevated glucose delivery; additional findings include cardiac hypertrophy, pulmonary edema, and cardiac dysfunction, which can potentially connect the transcriptional and DNA methylation alterations linked to long-term adverse CVD outcomes; and 4) the identification of chronic O-GlcNAc modifications that contribute to maladaptive cardiac responses, characterized by hypertrophy, exacerbated fibrosis, and transcriptomic changes, potentially lead to heart failure (HF). Collectively, these studies underscore the significant transcriptional and epigenetic diversity underlying various cardiac pathophysiological states. This dissertation lays foundational knowledge on the etiologies of HF, paving the way for in-depth mechanistic explorations and the development of precision-based therapeutic strategies.
ProQuest ID
Recommended Citation
Bakshi, Sayan, "Transcriptomic Transformations And Epigenetic Elements: The Heart Of The Matter Across Diverse Cardiac Pathophysiologies" (2025). All ETDs from UAB. 7289.
https://digitalcommons.library.uab.edu/etd-collection/7289
