Decrease of vascular smooth muscle cell locomotion by abciximab, but not tirofiban: a possible role of different affinity to alpha v beta 3 integrins

Blindt, Ruediger and Bosserhoff, Anja-Katrin and Krott, Nicole and Vogt, Felix and Hanrath, Peter and Demircan, Lütfü and vom Dahl, Jürgen (2002) Decrease of vascular smooth muscle cell locomotion by abciximab, but not tirofiban: a possible role of different affinity to alpha v beta 3 integrins. CORONARY ARTERY DISEASE, 13 (7). pp. 357-364. ISSN 0954-6928, 1473-5830

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Abstract

Aim 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 mug/ml), tirofiban (0.1-1 mug/ml), and the alpha v beta 3 specific antibody LM609 (1-5 mug/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, abcximab demonstrated a dose-dependent inhibition of migration (IC50 = 33 mug/ml) and invasion (IC50 = 0.5 mug/ml) of VSMCs. Administration during the assay without pre-treatment inhibited migration similarly (IC50 = 32 mug/ml) but invasion to a significant lower extent (IC50 = 44 mug/ml). Administration of tirofiban during the assay with or without pre-treatment had no inhibitory effect on VSMC migration and invasion. Pretreatment alone with one of the substances also did not alter VSMC migration or invasion. Conclusion 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.

Item Type: Article
Uncontrolled Keywords: IIB/IIIA RECEPTOR BLOCKADE; ALPHA-V-BETA-3 INTEGRIN; ALPHA-2-BETA-1 INTEGRIN; MYOCARDIAL-INFARCTION; GLYCOPROTEIN IIB/IIIA; MIGRATION; INHIBITION; THROMBOSPONDIN; PROLIFERATION; RESTENOSIS; restenosis; angioplasty; smooth muscle; extracellular matrix; cell culture
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 Sep 2021 14:35
Last Modified: 29 Sep 2021 14:35
URI: https://pred.uni-regensburg.de/id/eprint/39710

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