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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M700385-JLR200 on December 3, 2007

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Journal of Lipid Research, Vol. 49, 581-587, March 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

An apolipoprotein A-I mimetic dose-dependently increases the formation of preβ1 HDL in human plasma

Jason S. Troutt, William E. Alborn, Marian K. Mosior, Jiannong Dai, Anthony T. Murphy, Thomas P. Beyer, Youyan Zhang, Guoqing Cao and Robert J. Konrad1

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285

Published, JLR Papers in Press, December 3, 2007.

1 To whom correspondence should be addressed. e-mail: konrad_robert{at}lilly.com

Preβ1 HDL is the initial plasma acceptor of cell-derived cholesterol in reverse cholesterol transport. Recently, small amphipathic peptides composed of D-amino acids have been shown to mimic apolipoprotein A-I (apoA-I) as a precursor for HDL formation. ApoA-I mimetic peptides have been proposed to stimulate the formation of preβ1 HDL and increase reverse cholesterol transport in apoE-null mice. The existence of a monoclonal antibody (MAb 55201) and a corresponding ELISA method that is selective for the detection of the preβ1 subclass of HDL provides a means of establishing a correlation between apoA-I mimetic dose and preβ1 HDL formation in human plasma. Using this preβ1 HDL ELISA, we demonstrate marked apoA-I mimetic dose-dependent preβ1 HDL formation in human plasma. These results correlated with increases in band density of the plasma preβ1 HDL, when observed by Western blotting, as a function of increased apoA-I mimetic concentration. Increased preβ1 HDL formation was observed after as little as 1 min and was maximal within 1 h. Together, these data suggest that a high-throughput preβ1 HDL ELISA provides a way to quantitatively measure a key component of the reverse cholesterol transport pathway in human plasma, thus providing a possible method for the identification of apoA-I mimetic molecules.

Supplementary key words high density lipoprotein • cholesterol • reverse cholesterol transport

Abbreviations: apoA-I, apolipoprotein A-I; PK, pharmacokinetic


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