Anti-vascular cell adhesion molecule-1 and anti-very late antigen-4 monoclonal antibodies inhibit neointimal hyperplasia in the murine model of arterial injury.

摘要

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. METHODS AND 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. CONCLUSION: Anti-VCAM-1 and anti-VLA-4 mAbs prevent arterial neointimal formation after arterial injury.