Date of Award

12-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Food Technology

Committee Chair/Advisor

Alexis Stamatikos

Committee Member

Hannah Kate Wilson

Committee Member

Khaled Abdelaziz

Committee Member

George Cavender

Abstract

Atherosclerosis is the process of cholesterol buildup within arterial cells, which is considered a leading factor that causes certain cardiovascular diseases. Cholesterol accumulation within pro-inflammatory endothelial cells is thought to induce atherogenesis and accelerate atherosclerosis progression. Evidence suggests inhibiting the microRNA miR-33a in arterial cells may promote atheroprotection via increasing ABCA1 protein expression. MiR-33a is processed into two functional strands, miR-33a-5p and miR-33a-3p. The potential atheroprotective effect of inhibiting miR-33a-5p and/or miR-33a-3p precisely in pro-inflammatory endothelial cells is not fully understood, as data is scant regarding what potential atheroprotective impact ABCA1-dependent cholesterol within pro-inflammatory endothelial cells demonstrates, which occurs via miR-33a-5p/3p inhibition. My dissertation project investigates whether inhibiting miR-33a-5p/3p in cultured pro-inflammatory endothelial cells increases ABCA1-dependent cholesterol efflux. Initially, I transfected inflamed immortalized mouse aortic endothelial cells (iMAEC) with either the plasmid pAntimiR33a5p or the control plasmid pScr, and my results showed an increase for ABCA1-dependent cholesterol efflux within inflamed iMAEC transfected with pAntimiR33a5p versus inflamed control iMAEC. This effect was likely due to decreased miR-33a-5p expression occurring within inflamed iMAEC transfected with pAntimiR33a5p. I also transfected pro-inflammatory iMAEC with either pAntimiR33a3p or control plasmid pScr. For these experiments, I failed to observe increased ABCA1-dependent cholesterol efflux within inflamed endothelial cells transfected with pAntimiR33a3p, even though I still did detect a decrease in miR-33a-3p expression and increased ABCA1 mRNA expression in these transfected pro-inflammatory endothelial cells. Thus, inhibition of miR-33a-3p alone does not appear to recapitulate the same atheroprotective properties as inhibiting miR-33a-5p within these cells. Based on my findings, specifically inhibiting miR-33a-5p within the pro-inflammatory endothelium of atherogenic animal models may confer atheroprotection and so future studies should be conducted which assess atheroprotective efficacy of miR-33a-5p inhibition precisely occurring within the pro-inflammatory endothelial cells of atherogenic mice.

Included in

Food Science Commons

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.