Inhibition of vascular smooth muscle cell adhesion and migration by c7E3 Fab (abciximab): a possible mechanism for influencing restenosis

被引:29
作者
Baron, JH [1 ]
Moiseeva, EP
de Bono, DP
Abrams, KR
Gershlick, AH
机构
[1] Univ Leicester, Dept Med & Therapeut, Div Cardiol, Leicester, Leics, England
[2] Univ Leicester, Dept Epidemiol & Publ Hlth, Leicester LE1 7RH, Leics, England
关键词
extracellular matrix; monoclonal antibodies; receptors; restenosis; smooth muscle;
D O I
10.1016/S0008-6363(00)00201-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives: Brief intravenous administration of chimeric antibody c7E3 Fab during coronary angioplasty has been shown in some studies to provide long term protection against coronary events. Smooth muscle cell (SMC) adhesion and migration are key initial steps in the development of restenosis. The purpose of this study was to investigate the effect of c7E3 Fab on adhesion and migration of SMC to the extracellular matrix (ECM) proteins osteopontin (Opn) and vitronectin (Vn). Methods: Adhesion of human vascular SMCs to ECM proteins was quantified using a CyQUANT assay kit. Migration of SMCs to Vn, Opn and PDGF was studied using a modified Boyden's chamber migration assay. Integrin expression was determined by immunoprecipitation. Results: c7E3 Fab reduced SMC adhesion on Vn and Opn to 69.2+/-3.3% (P<0.001) and 52.5+/-4.8% (P<0.001) respectively, compared to adhesion without antibody present. This reduction was the same as that for anti-alpha (nu)beta (3) integrin antibody LM609 (P=0.5). The combination of anti-alpha (nu)beta (5) integrin antibody and c7E3 Fab had a greater effect than either antibody alone (P<0.001). c7E3 Fab reduced SMC migration to Vn and Opn to 51.6+/-8.9% (P<0.001) and 20.3+/-6.1% (P<0.001) respectively, compared to migration in the absence of antibodies. Again, similar results were seen with LM609. PDGF-induced SMC migration was also inhibited by c7E3 Fab (P=0.004) and LM609 (P=0.001), but to much less an extent. The migration SMCs from a culture found not to express the <alpha>(nu)beta (3) integrin was unaffected by these antibodies, strengthening the argument that c7E3 Fab inhibits SMC function via this integrin. Conclusions: c7E3 Fab inhibits the adhesion and migration of SMCs via the alpha (nu)beta (3) integrin. The inhibition, however, is partial, and varied depending on type of ECM protein and alpha (nu)beta (3) integrin expression. Some of the clinical benefits of c7E3 Fab may be due to its effect on SMCs. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:464 / 472
页数:9
相关论文
共 38 条
[1]   MANAGEMENT OF RESTENOSIS WITHIN THE PALMAZ-SCHATZ CORONARY STENT (THE UNITED-STATES MULTICENTER EXPERIENCE) [J].
BAIM, DS ;
LEVINE, MJ ;
LEON, MB ;
LEVINE, S ;
ELLIS, SG ;
SCHATZ, RA .
AMERICAN JOURNAL OF CARDIOLOGY, 1993, 71 (04) :364-366
[2]   In vitro evaluation of c7E3-Fab (ReoPro™) eluting polymer-coated coronary stents [J].
Baron, JH ;
Gershlick, AH ;
Hogrefe, K ;
Armstrong, J ;
Holt, CM ;
Aggarwal, RK ;
Azrin, M ;
Ezekowitz, M ;
de Bono, DP .
CARDIOVASCULAR RESEARCH, 2000, 46 (03) :585-594
[3]   Inhibition of vascular smooth muscle cell migration by peptide and antibody antagonists of the alpha(v)beta(3) integrin complex is reversed by activated calcium/calmodulin-dependent protein kinase II [J].
Bilato, C ;
Curto, KA ;
Monticone, RE ;
Pauly, RR ;
White, AJ ;
Crow, MT .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (03) :693-704
[4]   STIMULATION OF MIGRATION OF HUMAN AORTIC SMOOTH-MUSCLE CELLS BY VITRONECTIN - IMPLICATIONS FOR ATHEROSCLEROSIS [J].
BROWN, SL ;
LUNDGREN, CH ;
NORDT, T ;
FUJII, S .
CARDIOVASCULAR RESEARCH, 1994, 28 (12) :1815-1820
[5]   USE OF A MONOCLONAL-ANTIBODY DIRECTED AGAINST THE PLATELET GLYCOPROTEIN IIB/IIIA RECEPTOR IN HIGH-RISK CORONARY ANGIOPLASTY [J].
CALIFF, RM ;
SHADOFF, N ;
VALETT, N ;
BATES, E ;
GALEANA, A ;
KNOPF, W ;
SHAFTEL, J ;
BENDER, MJ ;
AVERSANO, T ;
RAQUENO, J ;
GURBEL, P ;
COWFER, J ;
COHEN, M ;
CROSS, P ;
BITTL, J ;
EDDINGS, K ;
TAYLOR, M ;
DEROSA, K ;
HATTEL, L ;
COOPER, L ;
ESHELMAN, B ;
FINTEL, D ;
NIEMYSKI, P ;
KLEIN, L ;
KENNEDY, H ;
THORNTON, T ;
KEREIAKES, D ;
MARTIN, L ;
ANDERSON, L ;
HIGBY, N ;
ELLIS, S ;
BREZINA, K ;
GEORGE, B ;
CHAPEKIS, A ;
SMITH, D ;
ANWAR, A ;
GERBER, TL ;
PRITCHARD, GL ;
MYLER, R ;
SHAW, R ;
MURPHY, M ;
WARD, K ;
MADIGAN, NP ;
BLANKENSHIP, J ;
HALBERT, M ;
FLANAGAN, C ;
TANNENBAUM, M ;
POLICH, M ;
STEVENSON, C ;
TCHENG, J .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 330 (14) :956-961
[6]   INHIBITION OF NEOINTIMAL HYPERPLASIA BY BLOCKING ALPHA(V)BETA(3), INTEGRIN WITH A SMALL PEPTIDE ANTAGONIST GPENGRGDSPCA [J].
CHOI, ET ;
ENGEL, L ;
CALLOW, AD ;
SUN, SP ;
TRACHTENBERG, J ;
SANTORO, S ;
RYAN, US .
JOURNAL OF VASCULAR SURGERY, 1994, 19 (01) :125-134
[7]   BETA-1 AND BETA-3 INTEGRINS HAVE DIFFERENT ROLES IN THE ADHESION AND MIGRATION OF VASCULAR SMOOTH-MUSCLE CELLS ON EXTRACELLULAR-MATRIX [J].
CLYMAN, RI ;
MAURAY, F ;
KRAMER, RH .
EXPERIMENTAL CELL RESEARCH, 1992, 200 (02) :272-284
[8]  
COLLER BS, 1985, BLOOD, V66, P1456
[9]   Vitronectin expression and interaction with receptors in smooth muscle cells from human atheromatous plaque [J].
Dufourcq, P ;
Louis, H ;
Moreau, C ;
Daret, D ;
Boisseau, MR ;
Lamazière, JMD ;
Bonnet, J .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (02) :168-176
[10]  
Ellis SG, 1999, CIRCULATION, V100, P799