Anti-vascular cell adhesion molecule-1 and anti-very late antigen-4 monoclonal antibodies inhibit neointimal hyperplasia in the murine model of arterial injury.
OBJECTIVE
Arterial restenosis after angioplasty limits long-term survival of patients. Murine arterial injury models develop neointimal hyperplasia similar to that observed in clinical coronary arterial restenosis after angioplasty. Adhesion of vascular cell adhesion molecule (VCAM)-1 and its ligand very late antigen (VLA)-4 plays an important role in neointimal formation after vascular injury.


RESULTS
To evaluate the effectiveness of blocking VCAM-1 and VLA-4 adhesion to prevent neointimal formation, mice with induced abdominal aortic injury were treated with the combined anti-VCAM-1 and anti-VLA-4 mAbs (n = 8) or not treated (n = 6). Injured arteries were harvested at day 14. Immunohistochemistry and in situ reverse transcriptase polymerase chain reaction were performed for detection of VCAM-1, intercellular adhesion molecule (ICAM)-1 and platelet-derived growth factor (PDGF)-B mRNA expression in the arteries. Arteries without treatment showed significant neointimal formation with enhancement of ICAM-1, VCAM-1 and PDGF-B mRNA, while expression of these and intimal thickening were almost nonexistent in the recipients of mAbs to VCAM-1 and VLA-4.


CONCLUSIONS
Anti-VCAM-1 and anti-VLA-4 mAbs prevent arterial neointimal formation after arterial injury.
Suzuki
Jun-ichi
J
Department of Cardiovascular Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Japan. jsuzuki.cvm@tmd.ac.jp
Izawa
Atsushi
A
Isobe
Mitsuaki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D006965:Hyperplasia / Q000517:prevention & control; D039041:Integrin alpha4beta1 / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D051379:Mice; D023421:Models, Animal; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000008:administration & dosage* / Q000276:immunology
D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1