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The Role of ACAT2 in the Initiation and Treatment of Atherosclerosis

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abstract
Hepatic acyl coenzyme A:cholesterol acyltransferase 2 (ACAT2) synthesizes cholesteryl ester (CE) from free cholesterol and fatty acyl-CoA. ACAT2 is responsible for the packaging of cholesteryl oleate (CO) into VLDL secreted from the liver and studies have shown a relationship between both ACAT2 activity and CO content of apoB-containing lipoproteins with atherosclerosis. The purpose of the studies was to extend our understanding of ACAT2 and primarily to elucidate its role in the initiation and treatment of atherosclerosis. To elucidate it's role in the initiation of atherosclerosis we proposed that as a result of elevated ACAT2 activity, more CO would be packaged into the low-density lipoprotein (LDL) core and resulting in a particle with a greater likelihood to be retained in the artery wall. To determine it's role in the treatment of atherosclerosis, we utilized an antisense oligonucleotide (ASO) to knockdown ACAT2 expression in the liver to determine how depleting atherogenic particles of CO would effect atherosclerotic lesion regression.
subject
ACAT2
Cholesteryl Oleate
Magnetic Resonance Imaging
Proteoglycan
Regression
contributor
Melchior, John Trevvett (author)
Rudel, Lawrence L (committee chair)
St. Clair, Richard W (committee member)
Temel, Ryan E (committee member)
Shelness, Gregory S (committee member)
Edwards, Iris J (committee member)
Link, Kerry M (committee member)
date
2012-06-12T08:36:02Z (accessioned)
2012-12-12T09:30:07Z (available)
2012 (issued)
degree
Molecular Pathology (discipline)
embargo
2012-12-12 (terms)
identifier
http://hdl.handle.net/10339/37294 (uri)
language
en (iso)
publisher
Wake Forest University
title
The Role of ACAT2 in the Initiation and Treatment of Atherosclerosis
type
Dissertation

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