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Effects of abciximab on key pattern of human coronary restenosis in vitro: impact of the SI/MPL-ratio.

AbstractBACKGROUND:
The significant reduction of angiographic restenosis rates in the ISAR-SWEET study (intracoronary stenting and antithrombotic regimen: is abciximab a superior way to eliminate elevated thrombotic risk in diabetes) raises the question of whether abciximab acts on clopidogrel-independent mechanisms in suppressing neointimal hyperplasia. The current study investigates the direct effect of abciximab on ICAM-1 expression, migration and proliferation.
METHODS:
ICAM-1: Part I of the study investigates in cytoflow studies the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 microg/ml) on TNF-alpha induced expression of intercellular adhesion molecule 1 (ICAM-1). Migration: Part II of the study explored the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 microg/ml) on migration of HCMSMC over a period of 24 h. Proliferation: Part III of the study investigated the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 microg/ml) on proliferation of HUVEC, HCAEC, and HCMSMC after an incubation period of 5 days.
RESULTS:
ICAM-1: In human venous endothelial cells (HUVEC), human coronary endothelial cells (HCAEC) and human coronary medial smooth muscle cells (HCMSMC) no inhibitory or stimulatory effect on expression of ICAM-1 was detected. Migration: After incubation of HCMSMC with abciximab in concentrations of 0.0002-2 microg/ml a stimulatory effect on cell migration was detected, statistical significance was achieved after incubation with 0.002 microg/ml (p < 0.05), 0.002 microg/ml (p < 0.001), and 0.2 microg/ml (p < 0.05). Proliferation: Small but statistically significant antiproliferative effects of abciximab were detected after incubation of HUVEC (0.02 and 2.0 microg/ml; p = 0.01 and p < 0.01), HCAEC (2.0 and 20.0 microg/ml; p < 0.05 and p < 0,01), and HCMSMC (2.0 and 20.0 microg/ml; p < 0.05 and p < 0.05). The significant inhibition (SI) of cell proliferation found in HCAEC and HCMSMC was achieved with drug concentrations more than 10 times beyond the maximal plasma level (MPL), resulting in a SI/MPL-ratio > 1.
CONCLUSION:
Thus, the anti-restenotic effects of systemically administered abciximab reported in the ISAR-SWEET-study were not caused by a direct inhibitory effect on ICAM-1 expression, migration or proliferation.
AuthorsRainer Voisard, Mustafa Alan, Lutz von Müller, Regine Baur, Vinzenz Hombach
JournalBMC cardiovascular disorders (BMC Cardiovasc Disord) Vol. 6 Pg. 14 (Apr 04 2006) ISSN: 1471-2261 [Electronic] England
PMID16595000 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Immunoglobulin Fab Fragments
  • Intercellular Adhesion Molecule-1
  • Abciximab
Topics
  • Abciximab
  • Antibodies, Monoclonal (administration & dosage, blood, pharmacology)
  • Cell Movement (drug effects)
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Cells, Cultured
  • Coronary Restenosis (prevention & control)
  • Coronary Vessels (cytology)
  • Dose-Response Relationship, Drug
  • Endothelial Cells (cytology, metabolism)
  • Humans
  • Immunoglobulin Fab Fragments (administration & dosage, blood, pharmacology)
  • Intercellular Adhesion Molecule-1 (metabolism)
  • Muscle, Smooth, Vascular (cytology)
  • Myocytes, Smooth Muscle (cytology, metabolism)
  • Umbilical Veins (cytology)

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