Date of Award

8-2026

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Food, Nutrition, and Culinary Science

Committee Chair/Advisor

Dr. Alexis Stamatikos

Committee Member

Dr. Renee Cottle

Committee Member

Dr. James Sternberg

Abstract

Atherosclerosis is one of the major causes of cardiovascular disease, characterized by the accumulation of cholesterol and foam cells within the arterial walls. Foam cells were traditionally believed to originate from macrophages; however, recent studies have shown vascular smooth muscle cells are also capable of accumulating cholesterol and developing foam-cell-like characteristics. ATP-binding cassette transporter A1 (ABCA1) plays an important role in removing excess cholesterol from cells by transporting intracellular cholesterol to circulatory apolipoprotein A-I (apoAI). MicroRNA-33a (miR-33a) is known to suppress ABCA1 expression and limit cholesterol efflux. However, its role in primary aortic smooth muscle cells is unknown and not fully understood. This thesis project investigated whether deleting miR-33a increases ABCA1 expression and apoAI-mediated cholesterol efflux in primary mouse aortic smooth muscle cells. Primary aortic smooth muscle cells were isolated from miR-33a floxed mice and characterized, then transduced with a Cre-expressing lentivirus to ablate miR-33a. Lentiviral transduction successfully reduced miR-33a-3p and miR-33a-5p expression. Upon ablation of miR-33a, we observed an increase in ABCA1 mRNA and protein expression as well as enhanced apoAI-mediated cholesterol efflux in primary aortic smooth muscle cells. These findings suggest that miR-33a limits cholesterol efflux in primary aortic smooth muscle cells by suppressing ABCA1 activity. Directly targeting miR-33a in arterial smooth muscle may therefore provide a potential atheroprotective approach via improving cholesterol efflux within arterial smooth muscle cells, which may lead to either treating atherosclerosis and/or preventing this disease.

Included in

Nutrition Commons

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