Vitaxin, a humanized monoclonal antibody to the vitronectin receptor (alphavbeta3), reduces neointimal hyperplasia and total vessel area after balloon injury in hypercholesterolemic rabbits.

Abstract

The vitronectin receptor (alphavbeta3) mediates several biological processes that are critical to the formation of a neointima after coronary interventions. Blockade of alphavbeta3 could reduce neointima formation by inhibiting smooth muscle cell migration, decreasing transforming growth factor-beta1 expression, enhancing apoptosis, or reducing neovasculature. The effects of short-term administration of Vitaxin, a humanized monoclonal antibody to alphavbeta3, on the responses to balloon injury were tested in hyperlipidemic rabbits. Balloon angioplasty was performed on the iliac arteries of male New Zealand White rabbits that were fed an atherogenic diet for 1 week before injury and until euthanization at 4 weeks. Rabbits were given either saline (control) or 1 of 2 dosing regimens of Vitaxin (high dose, 5.0 mg/kg, and low dose, 0.5 mg/kg), which were administered intra-arterially before injury and intramuscularly on days 2 and 3. High-dose and low-dose Vitaxin were equally effective in decreasing neointima formation even in the presence of hypercholesterolemia, a stimulus to alphavbeta3 expression. Vitaxin reduced transforming growth factor-beta1 and enhanced apoptosis in injured arteries. Despite these positive effects, Vitaxin administration was associated with a reduction in artery size, indicating a negative effect on remodeling. Vitaxin has a potential role in preventing intimal hyperplasia, especially if the negative effects on remodeling can be overcome, by dose adjustment or other strategies.

• Authors: K R Coleman, G A Braden, M C Willingham, D C Sane
• Journal: Circulation research (Circ Res) Vol. 84 Issue 11 Pg. 1268-76 (Jun 11 1999) ISSN: 0009-7330 [Print] United States
• PMID: 10364564 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Receptors, Vitronectin
• Transforming Growth Factor beta
• etaracizumab
• Cholesterol

Topics

• Angioplasty, Balloon (adverse effects)
• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Apoptosis (physiology)
• Cell Movement (physiology)
• Cholesterol (metabolism)
• Fluorescent Antibody Technique
• Humans
• Hypercholesterolemia (therapy)
• Hyperplasia (therapy)
• Iliac Artery (injuries, pathology)
• Male
• Rabbits
• Receptors, Vitronectin (immunology)
• Transforming Growth Factor beta (metabolism)
• Tunica Intima (injuries, pathology)