An apolipoprotein A-I mimetic dose-dependently increases the formation of prebeta1 HDL in human plasma.
Prebeta1 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 prebeta1 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 prebeta(1) subclass of HDL provides a means of establishing a correlation between apoA-I mimetic dose and prebeta1 HDL formation in human plasma. Using this prebeta1 HDL ELISA, we demonstrate marked apoA-I mimetic dose-dependent prebeta1 HDL formation in human plasma. These results correlated with increases in band density of the plasma prebeta1 HDL, when observed by Western blotting, as a function of increased apoA-I mimetic concentration. Increased prebeta1 HDL formation was observed after as little as 1 min and was maximal within 1 h. Together, these data suggest that a high-throughput prebeta1 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.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Jason S
JS
Troutt
William E
WE
Alborn
Marian K
MK
Mosior
Jiannong
J
Dai
Anthony T
AT
Murphy
Thomas P
TP
Beyer
Youyan
Y
Zhang
Guoqing
G
Cao
Robert J
RJ
Konrad
D016632:Apolipoprotein A-I; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D053442:High-Density Lipoproteins, Pre-beta / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D018716:Molecular Mimicry; D010455:Peptides / Q000494:pharmacology*
D016632:Apolipoprotein A-I; D053442:High-Density Lipoproteins, Pre-beta; D010455:Peptides; D002784:Cholesterol