Date of Award
4-30-2024
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Pharmacology and Experimental Therapeutics
First Advisor
Walter Jones
Second Advisor
Joanna Bakowska
Abstract
Extracellular vesicles (EVs) are membranous vesicles secreted by most cells. They contain lipids, proteins, and nucleic acids, including microRNAs (miRNA), and function in intercellular communication by endocytosis into other cells. EVs in diseased states carry miRNAs and proteins reflective of the changed state of cells and can be endocytosed into other cells to exert regulatory effects. Thus, EVs represent a form of paracrine genetic regulation in health and disease. Myocardial infarction (MI) and pulmonary embolism (PE) are leading causes of cardiovascular deaths worldwide. It is important to develop new diagnostic and therapeutic approaches that could lead to medical advances. Circulating miRNAs have been studied as gene expression regulators and biomarkers for different diseases. Many miRNAs were identified as potential biomarkers for PE, but most lack specificity. The central hypothesis is that EVs in diseased state carry different miRNA cargo reflective of the pathology, travel via circulation and/or other fluids, and that EVs are taken up by target cells via specific mechanisms and affect gene expression in those cells. Due to technical limitations, no study has been able to track EV secretion and uptake in single disease. We propose to study EV secretion and uptake in two disease models. Aim 1 will determine the changes in circulating EV miRNA profile during PE. To address the current lack of specificity in diagnostic biomarkers for PE, we used a more efficient EV isolation method from plasma and identified different miRNA expressions in the EVs between healthy and PE patients. Aim 2 will determine the mechanisms of MSC EV miRNA cargo transfer to recipient cardiac cells. Evidence suggests that MSC EVs are cardioprotective in MI largely due to their miRNA cargos and this Aim examines the role of macropinocytosis and clathrin-mediated endocytosis in this process.
Recommended Citation
Zhang, Chongyu, "The Role of Extracellular Vesicles and Their Cargo in Intercellular Communication" (2024). Dissertations. 4096.
https://ecommons.luc.edu/luc_diss/4096
