In vitro biomarker discovery for atherosclerosis by proteomics

被引:79
作者
Fach, EM [1 ]
Garulacan, LA [1 ]
Gao, J [1 ]
Xiao, Q [1 ]
Storm, SM [1 ]
Dubaquie, YP [1 ]
Hefta, SA [1 ]
Opiteck, GJ [1 ]
机构
[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Clin Discovery, Princeton, NJ 08543 USA
关键词
D O I
10.1074/mcp.M400160-MCP200
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1200 / 1210
页数:11
相关论文
共 70 条
[61]  
TAPPER H, 1990, BIOCHEM J, P2
[62]   Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes [J].
Tsimikas, S ;
Bergmark, C ;
Beyer, RW ;
Patel, R ;
Pattison, J ;
Miller, E ;
Juliano, J ;
Witztum, JL .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2003, 41 (03) :360-370
[63]  
Tsimikas S, 2001, CIRCULATION, V103, P1930
[64]  
TSUCHIYA S, 1982, CANCER RES, V42, P1530
[65]  
Vallabhajosula S, 1997, J NUCL MED, V38, P1788
[66]   Macrophages stimulate cholesteryl ester accumulation in cocultured smooth muscle cells incubated with lipoprotein-proteoglycan complex [J].
Vijayagopal, P ;
Glancy, DL .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1996, 16 (09) :1112-1121
[67]   MAPPING OF PROTEOGLYCANS IN ATHEROSCLEROTIC LESIONS [J].
VOLKER, W ;
SCHMIDT, A ;
OORTMANN, W ;
BROSZEY, T ;
FABER, V ;
BUDDECKE, E .
EUROPEAN HEART JOURNAL, 1990, 11 :29-40
[68]   Oxidized low-density lipoprotein regulates matrix metalloproteinase-9 and its tissue inhibitor in human monocyte-derived macrophages [J].
Xu, XP ;
Meisel, SR ;
Ong, JM ;
Kaul, S ;
Cercek, B ;
Rajavashisth, TB ;
Sharifi, B ;
Shah, PK .
CIRCULATION, 1999, 99 (08) :993-998
[69]   Lysosomal destabilization during macrophage damage induced by cholesterol oxidation products [J].
Yuan, XM ;
Li, W ;
Brunk, UT ;
Dalen, H ;
Chang, YH ;
Sevanian, A .
FREE RADICAL BIOLOGY AND MEDICINE, 2000, 28 (02) :208-218
[70]   Endogenously produced glycosaminoglycans affecting the release of lipoprotein lipase from macrophages and the interaction with lipoproteins [J].
Zimmermann, R ;
Sartipy, P ;
Winkler, R ;
Zechner, R ;
Hurt-Camejo, E ;
Kostner, GM .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1484 (2-3) :316-324