Submitted on August 27, 2007
Revised on November 28, 2007
Accepted on December 3, 2007
An apolipoprotein A1 mimetic dose-dependently increases formation of pre-
1 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. Konrad
Experimental Medicine, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285
Corresponding Author: konrad_robert{at}lilly.com
Pre-beta1 HDL is the initial plasma acceptor of cell-derived cholesterol in reverse cholesterol transport (RCT). Recently, small amphipathic peptides comprised of D-amino acids have been shown to mimic Apolipoprotein A1 (ApoA1) as a precursor for HDL formation. ApoA1 mimetic peptides have been proposed to stimulate the formation of pre-beta1 HDL and increase RCT in ApoE null mice. The existence of a monoclonal antibody (MAb 55201) and a corresponding ELISA method that is selective for detection of the pre-beta1 subclass of HDL provides a means of establishing a correlation between ApoA1 mimetic dose and pre-beta1 HDL formation in human plasma. Using this pre-beta1 HDL ELISA, we demonstrate marked ApoA1 mimetic dose-dependent pre-beta1 HDL formation in human plasma. These results correlated with increases in band density of the plasma pre-beta1 HDL when observed by Western blotting, as a function of increased ApoA1 mimetic concentration. Increased pre-beta1 HDL formation was observed after as little as 1 minute and was maximal within one hour. Together, these data suggest that a high-throughput pre-beta1 HDL ELISA provides a way to quantitatively measure a key component of the RCT pathway in human plasma, thus providing a possible method for identification of ApoA1 mimetic molecules.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
