In vitro biomarker discovery for atherosclerosis by proteomics.
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. 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 with low-density lipoprotein (LDL). Analysis of the proteins contained in the cell supernatant using proteome scanning technology identified 59 proteins as being increased, 57 with no statistically measurable difference, and 17 decreasing in abundance following treatment with oxidized LDL, as compared with LDL. From the up-regulated list, proteins were prioritized based on their analytical confidence as well as their relevance to atherosclerosis pathways. Within the group of increased abundance, seven families 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.
Fach
Estelle M
EM
Department of Clinical Discovery, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Princeton, NJ 08543-5400, USA. estelle.fach@bms.com
Garulacan
Leah-Ann
LA
Gao
Ji
J
Xiao
Qing
Q
Storm
Stephen M
SM
Dubaquie
Yves P
YP
Hefta
Stanley A
SA
Opiteck
Gregory J
GJ
D000595:Amino Acid Sequence; D001161:Arteriosclerosis / Q000378:metabolism*; D015415:Biomarkers / Q000737:chemistry*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D021983:Cyclophilins / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003720:Densitometry; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D013058:Mass Spectrometry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D051116:Receptors, Scavenger; D013997:Time Factors; D015854:Up-Regulation
D015415:Biomarkers; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C081786:cyclophilin B; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; D020780:Matrix Metalloproteinase 9; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase