INHIBITION OF INTIMAL HYPERPLASIA AFTER BALLOON INJURY BY ANTIBODIES TO INTERCELLULAR-ADHESION MOLECULE-1 AND LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1

Background Although intercellular adhesion molecule-1 (ICAM-1) is know n to be expressed in balloon-injured arteries, it remains unknown whet her ICAM-1 plays a role in the progression of intimal hyperplasia (IH) induced by balloon injury. Methods and Results We examined the ICAM-1 expression in rat carotid arteries at 1, 2, 5, 7, 10, and 14 days aft er injury by immunohistochemistry. Medial smooth muscle cells (SMC) ex pressed ICAM-1 intensely at 1 to 2 days after injury. The regenerating endothelial cells expressed ICAM-1 more than did those of intact caro tid arteries. To investigate the effects of monoclonal antibodies (MAb s) on IH, we examined the intima/medial ratio of arteries at 2 weeks a fter injury in five treatment groups: nonimmune IgG, anti-membrane gly coprotein MAb, anti-lymphocyte function-associated antigen-1 (LFA-1) M Ab, anti-ICAM-1 MAb, and anti-ICAM/LFA-1 MAb. Treatments were administ ered intravenously into rats for 6 consecutive days after injury. MAb against LFA-1 alone or membrane glycoprotein had no effect on IH. The intima/media ratios in anti-ICAM-1 MAb-treated and anti-ICAM-1/LFA-1 M Ab-treated animals were significantly less than those in nonimmune IgG -treated and anti-membrane glycoprotein MAb-treated animals (P < .05). Conclusions Balloon injury induced or upregulated the ICAM-1 expressi on on vascular SMC and on regenerating endothelial cells. MAb against ICAM-1 or ICAM-1/LFA-1 attenuated IH. These results suggest that ICAM- 1 may play a role in the progression of IH after injury in rats.