Item Details

title

THE ROLE OF HEPATOCYTE ATP-BINDING CASSETTE TRANSPORTER A1 (ABCA1) AND APOLIPOPROTEIN M (APOM) IN HIGH DENSITY LIPOPROTEIN (HDL) METABOLISM

author

Bashore, Alexander Cusa

abstract

Hepatic ATP binding cassette transporter A1 (ABCA1) and apolipoprotein M (apoM) both have been shown to influence high density lipoprotein (HDL) metabolism. Hepatic ABCA1, a plasma membrane protein, functions to transport free cholesterol (FC) and phospholipids across the plasma membrane to apolipoproteins, forming nascent HDL particles. Hepatic ABCA1 is essential in HDL particle formation and maintenance of plasma HDL cholesterol (HDL-C) levels. However, its role in trafficking of hepatic FC into plasma versus bile for reverse cholesterol transport (RCT) is poorly understood. We found that hepatocyte specific ABCA1 knockout (HSKO) mice have increased plasma HDL cholesteryl ester (CE) clearance, selective uptake, and fecal excretion compared to control mice and these increases are mediated by increased hepatic LDLr expression. ABCA1 deletion also resulted in diminished recycling of HDL-C taken up by the liver back into plasma. Hepatocyte ABCA1 deletion unmasks a novel and selective FC trafficking pathway in which increased LDLr expression accelerates plasma HDL selective CE uptake by the liver and promotes HDL RCT into feces, consequently reducing HDL-derived hepatic FC recycling into plasma.

subject

Apolipoprotein

Cholesterol

High Density Lipoprotein

Lipids

Metabolism

contributor

Parks, John S (committee chair)

Tallant, Elisabeth A (committee member)

Kavanagh, Kylie (committee member)

Liu, Mingxia (committee member)

Zhu, Xuewei (committee member)

date

2019-01-11T09:35:19Z (accessioned)

2024-01-10T09:30:06Z (available)

2018 (issued)

degree

Physiology and Pharmacology (discipline)

embargo

2024-01-10 (terms)

identifier

http://hdl.handle.net/10339/93058 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation