Keywords

Cardiology, Heart disease, Ischemia, Post-translational modifications, Acetylation

Abstract

The most common cause of death is cardiovascular disease, with a prevalence of 3,500 per 100,000 people worldwide (Pirani and Khiavi 2017). Tissue ischemia due to cardiovascular diseases induces disorder such as myocardial infarction, pulmonary arterial hypertension, and atherosclerosis. In ischemic cardiomyopathy, heart failure is caused by the cardiac muscle getting damaged due to ischemia and losing its ability to pump blood properly. These ischemic conditions can affect cellular homeostasis and metabolism, which can result in cardiovascular dysfunction. Considering the effect of ischemic cardiomyopathy on the global population, it is vital to understand the impact of ischemia on the cardiac cells and how ischemic condition changes different cellular functions through epigenetic changes.

Epigenetics has been associated with some cardiovascular disease risk factors, so reversing or modifying these changes through drug therapy could reverse or prevent the effects of CVD. A combination of genetics and environmental factors can regulate gene expression dynamically on a physiological level. Additionally, post-translational modifications (PTM) play an important role in cellular gene expression through epigenetic changes.

Neonatal rat primary cardiomyocytes were used to understand the changes in acetylation during ischemic conditions compared to normoxic conditions. Mass spectrometry was performed on proteins isolated from these samples to analyze changes in acetylation due to ischemia. Analysis was performed to link genomic information with higher-order functional information for the identified proteins. These acetylated changes were found to be localized in different subcellular organelles and involved various molecular functions and biological processes. This study aims to identify global acetylation changes in cells exposed to ischemic conditions to identify therapeutic targets to prevent and treat ischemia-mediated heart disease.

Thesis Completion Year

2024

Thesis Completion Semester

Spring

Thesis Chair

Manish, Gupta

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Medicine

Language

English

Access Status

Campus Access

Length of Campus Access

3 years

Campus Location

Orlando (Main) Campus

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