on May 25, 2006
Published online before print May 25, 2006, doi: 10.1161/01.ATV.0000229219.13757.a2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on December 8, 2005
Accepted on April 27, 2006
Hepatic ATP-Binding Cassette Transporter A1 Is a Key Molecule in High-Density Lipoprotein Cholesteryl Ester Metabolism in Mice
Roshni R. Singaraja ;
From the University of British Columbia (R.R.S., N.B., M.K., M.R.H.), Vancouver, Canada; University Hospital Eppendorf (B.S., M.B., M.M., J.H., F.R.), Hamburg, Germany; Wake Forest University (J.M.T., J.S.P.), Winston-Salem, NC; and Columbia University (R.R.), New York, NY.
* To whom correspondence should be addressed. E-mail: Rinninger{at}uke.uni-hamburg.de.
Objective--Mutations in ATP-binding cassette transporter A1 (ABCA1), the cellular lipid transport molecule mutated in Tangier disease, result in the rapid turnover of high-density lipoprotein (HDL)-associated apolipoproteins that presumably are cleared by the kidneys. However, the role of ABCA1 in the liver for HDL apolipoprotein and cholesteryl ester (CE) catabolism in vivo is unknown.
Methods and Results--Murine HDL was radiolabeled with 125I in its apolipoprotein and with [3H]cholesteryl oleyl ether in its CE moiety. HDL protein and lipid metabolism in plasma and HDL uptake by tissues were investigated in ABCA1-overexpressing BAC-transgenic (BAC+) mice and in mice harboring deletions of total (ABCA1-/-) and liver-specific ABCA1 (ABCA1-L/-L). In BAC+ mice with elevated ABCA1 expression, fractional catabolic rates (FCRs) of both the protein and the lipid tracer were significantly decreased in plasma and in the liver, yielding a diminished hepatic selective CE uptake from HDL. In contrast, ABCA1-/- or ABCA1-L/-L mice had significantly increased plasma and liver FCRs for both HDL tracers. An ABCA1 deficiency was associated with increased selective HDL CE uptake by the liver under all experimental conditions.
Conclusions--Hepatic ABCA1 has a critical role for HDL catabolism in plasma and for HDL selective CE uptake by the liver.
Key words: ABCA1 • HDL • selective uptake • cholesteryl ester
This article has been cited by other articles:
 |
|
 |
|
  R. L. Jacobs, S. Lingrell, Y. Zhao, G. A. Francis, and D. E. Vance Hepatic CTP:Phosphocholine Cytidylyltransferase-{alpha} Is a Critical Predictor of Plasma High Density Lipoprotein and Very Low Density Lipoprotein J. Biol. Chem., January 25, 2008; 283(4): 2147 - 2155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-D. Wang, V. Franklin, M. Sundaram, R. S. Kiss, K. Ho, M. Gallant, and Y. L. Marcel Differential Regulation of ATP Binding Cassette Protein A1 Expression and ApoA-I Lipidation by Niemann-Pick Type C1 in Murine Hepatocytes and Macrophages J. Biol. Chem., August 3, 2007; 282(31): 22525 - 22533. [Abstract] [Full Text] [PDF]
|
|