Optimizing Endothelial Cell Specific Polymersome-Based Atheroprotective Therapies

Author

Ally C. Brawner, Clemson UniversityFollow

Date of Award

12-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Food, Nutrition, and Culinary Science

Committee Chair/Advisor

Alexis Stamatikos

Committee Member

Jessica Larsen

Committee Member

Paul Dawson

Abstract

Atherosclerotic cardiovascular disease is the number one cause of death in the United States and the world. Every year, billions of dollars are spent in the US alone for direct treatments of this disease, especially on prescription medicines like statins. However, these medications have been unable to curtail global mortality rates, partially because they do not target the entirety of atherosclerotic pathophysiology. A key area of this pathophysiology is that atheroprone arteries typically include pro-inflammatory endothelial cells that exhibit decreased levels of apoAI-mediated cholesterol efflux and an increased release of adhesion molecules, such as VCAM-1. The objective of my project was to develop a novel cell-specific system for delivering atheroprotective plasmid DNA to pro-inflammatory endothelial cells. In my investigation, we utilized endothelial cell VCAM-1 as a delivery target via using VHPK peptide-decorated polymersomes, and we employed an anti-miR-33a-5p expressing plasmid to decrease the expression of cellular miR-33a-5p, which in turn could lead to increased expression of ABCA1, which may enhance apoAI-mediated cholesterol efflux. We found that polymersome delivery of anti-miR-33a-5p expressing plasmid DNA to pro-inflammatory endothelial cells resulted in lower expression of miR-33a-5p, higher expression ofABCA1, and enhanced levels of apoAI-mediated cholesterol efflux. These results indicate that this peptide-decorated polymersome delivery method of anti-miR-33a-5p expressing plasmid DNA appears to be atheroprotective via enhancing apoAI-mediated cholesterol efflux in pro-inflammatory endothelial cells.

Recommended Citation

Brawner, Ally C., "Optimizing Endothelial Cell Specific Polymersome-Based Atheroprotective Therapies" (2025). All Theses. 4625.
https://open.clemson.edu/all_theses/4625