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Submitted on October 12, 2004
Revised on October 20, 2004
Accepted on October 20, 2004

In vitro biomarker discovery for atherosclerosis by proteomics

Estelle M. Fach, Leah-Ann Garulacan, Ji Gao, Qing Xiao, Stephen M. Storm, Yves P. Dubaquie, Stanley A. Hefta, and Gregory J. Opiteck

Clinical Discovery Technologies, Bristol Myers Squibb, Pennington, NJ 08648

Corresponding Author: estelle.fach{at}bms.com

Summary Objective: The purpose of this study was to identify in vitro and then prioritize a tractable set of protein biomarker candidates of atherosclerosis that may eventually be developed to measure the extent, progression, regression and stability of atherosclerotic lesions. Methods and results: A study was conducted using an in vitro “foam cell” model based on the stimulation of differentiated THP1 cells with oxidized low density lipoprotein (oxidized LDL) as compared to low density lipoprotein (LDL). Analysis of the proteins contained in the cell supernatant using proteome scanning technology identified fifty-nine proteins as being increased, fifty-seven with no statistically measurable difference, and seventeen decreasing in abundance following treatment with oxidized LDL, as compared to LDL. From the upregulated list, proteins were prioritized based on their analytical confidence as well as their relevance to atherosclerosis pathways. Conclusions: Within the group of increased abundance, seven family of proteins were of particular interest: fatty acid-binding proteins, chitinase-like enzymes, cyclophilins, cathepsins, proteoglycans , urokinase–type plasminogen activator receptor and a macrophage scavenger receptor.


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