title: Inhibition of vascular smooth muscle cell adhesion and migration by c7E3 Fab (abciximab): a possible mechanism for influencing restenosis.
abstract: OBJECTIVE
  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(v)beta(3) integrin antibody LM609 (P=0.5). The combination of anti-alpha(v)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(v)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(v)beta(3) integrin. The inhibition, however, is partial, and varied depending on type of ECM protein and alpha(v)beta(3) integrin expression. Some of the clinical benefits of c7E3 Fab may be due to its effect on SMCs.
authors.affiliation: Division of Cardiology, Department of Medicine and Therapeutics, University of Leicester, Leicester, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Baron
authors.forename: E P
authors.initials: EP
authors.lastname: Moiseeva
authors.forename: D P
authors.initials: DP
authors.lastname: de Bono
authors.forename: K R
authors.initials: KR
authors.lastname: Abrams
authors.forename: A H
authors.initials: AH
authors.lastname: Gershlick
mesh_terms: D000077284:Abciximab; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003327:Coronary Disease / Q000517:prevention & control*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D053495:Osteopontin; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000276:immunology; D012008:Recurrence; D012501:Saphenous Vein; D012795:Sialoglycoproteins / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D019030:Receptors, Vitronectin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D019096:Vitronectin; D053495:Osteopontin; D000077284:Abciximab