Abciximab inhibits the migration and invasion potential of human coronary artery smooth muscle cells

In the EPIC trial, high-risk patients received the integrin receptor antago nist abciximab v placebo during and for 12 h following percutaneous coronar y intervention with a significant 23% decrease of repeat revascularisation at 6 months. However, EPILOG and CAPTURE trials could not confirm these pro mising long-term results. Recently presented data from the EPISTENT trial s uggested a beneficial effect of abciximab on restenosis in patients with di abetes. Based on these divergent results the aim of this study was to test whether alphav beta3 receptor blockade by abciximab could cause inhibition of human coronary smooth muscle cell (hcSMC) proliferation, migration, and invasion which represent crucial steps during restenosis development, In co ntrast to quiescent hcSMCs, proliferating cells were capable to migrate tow ards chemoattractive stimuli and even capable to invade through a basement membrane equivalent. Abciximab and LM609, an alphav beta3 specific inhibiti ng antibody. caused only a modest dose-dependent inhibition of hcSMC prolif eration. On the contrary, the chemotactic and invasive potential of hcSMCs was significantly inhibited by abciximab administration 24 h prior to and d uring migration. (IC50 = 33.0 mug/ml for chemotaxis and IC50 = 0.5 mug/ml f or invasion). For LM609 similar results were obtained, Administration of th e drugs just during migration without pretreatment inhibited migration equa lly but invasion to a lower extent (abciximab: IC50 = 32.6 mug/ml for chemo taxis and IC50 = 44.9 mug/ml for invasion; LM609 IC50 = 3.1 mug/ml for chem otaxis and IC50 = 2.0 mug/ml for invasion). The attachment to the extracell ular matrix proteins collagen I, collagen TV, laminin and vitronectin was n ot influenced. Pretreatment for 24 h with abciximab or LM609 did not cause a downregulation of the alphav beta3-integrin receptor. The results of this study indicate that the alphav beta3 antagonist abciximab is a potent inhi bitor of hcSMC migration and invasion which could explain the observed lowe r reintervention rate after PTCA and stent implantation (C) 2000 Academic P ress.