Decrease of vascular smooth muscle cell locomotion by abciximab, but not tirofiban: a possible role of different affinity to alpha v beta 3 integrins.
OBJECTIVE
The EPISTENT and EPIC studies demonstrated a reduction of clinically driven re-interventions after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation in patients treated with abciximab, while for tirofiban no similar effects could be demonstrated. This may be explained by the different effects on the migratory and invasive potential of vascular smooth muscle cells (VSMCs) by integrin alpha v beta 3 blockade. Therefore, the objective of this study was to compare the effectiveness of abciximab and tirofiban to affect VSMC migration and invasion.


METHODS
Vascular smooth muscle cells were treated with abciximab (0.1-1 microg/ml), tirofiban (0.1-1 microg/ml), and the alpha v beta 3 specific antibody LM609 (1-5 microg/ml), that was used as a positive control during the assay (treatment) over 24 h before the assay (pre-treatment), or before and during the assay (combined treatment). Sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxyy-6-nitro) benzene sulfonic acid (XTT)-assay and cell counting measured the influence of the substances on VSMC proliferation. Using a Boyden Chamber model, the capability of VSMCs for migration and invasion was tested with different chemo-attractants and barriers.


RESULTS
Any influence of the platelet glycoprotein (GP) IIb/IIIa receptor (integrin alpha IIb beta 3) antagonists on VSMC proliferation could be excluded. After combined treatment, abciximab demonstrated a dose-dependent inhibition of migration (IC50 = 33 microg/ml) and invasion (IC50 = 0.5 microg/ml) of VSMCs. Administration during the assay without pre-treatment inhibited migration similarly (IC50 = 32 microg/ml) but invasion to a significant lower extent (IC50 = 44 microg/ml). Administration of tirofiban during the assay with or without pre-treatment had no inhibitory effect on VSMC migration and invasion. Pre-treatment alone with one of the substances also did not alter VSMC migration or invasion.


CONCLUSIONS
Abciximab administration in physiological concentrations was capable of significantly inhibiting the migratory and invasive potential of VSMCs, while for tirofiban no similar effect could be demonstrated.
Blindt
Rüdiger
R
University Hospital, Aachen, Medical Clinic I, Regensburg, Germany. ruediger.blindt@post.rwth-aachen.de
Bosserhoff
Anja-Katrin
AK
Krott
Nicole
N
Vogt
Felix
F
Hanrath
Peter
P
Demircan
Lütfü
L
vom Dahl
Jürgen
J
D000077284:Abciximab; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001667:Binding, Competitive; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002633:Chemotaxis; D003331:Coronary Vessels; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D039302:Integrin alphaVbeta3 / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D039302:Integrin alphaVbeta3; D014443:Tyrosine; D000077466:Tirofiban; D000077284:Abciximab