INTIMAL HYPERPLASIA AFTER BALLOON INJURY IS ATTENUATED BY BLOCKING SELECTINS

Background Cell adhesion molecules facilitate the adherence of platele ts and leukocytes to the vascular endothelium in response to injury. R estenosis after balloon angioplasty is thought to represent the respon se to vascular injury. The role of cell adhesion in this process is un clear. Methods and Results This study was performed in New Zealand Whi te rabbits that underwent balloon angioplasty of the iliac artery. Exp ression of the cell adhesion molecule E-selectin on endothelium was de termined by immunohistochemistry and increased at 6 hours with a peak expression 24 to 48 hours after balloon injury, returning to baseline by 1 week. The expression of L-selectin on circulating leukocytes, mea sured by flow cytometry, was significantly increased at 48 hours, with return to baseline by 1 week. In seven animals, the selectins were bl ocked with an analogue of sialyl-Lewis(x) given as an IV bolus of 10 m g/kg followed by 2 mg.kg(-1).h(-1) IP infusion for 7 days. After 4 wee ks, compared with control animals, the study group had a larger lumen area (57.7 versus 44.7 mm(2), P < .05), smaller intima area (9.0 versu s 19.2 mm(2), P < .01), smaller intima/media ratio (0.4 versus 1.0, P < .01), and a smaller percent area stenosis (15.6% versus 34.3%, P < . 01). Conclusions The cell adhesion molecules E-selectin and L-selectin are expressed after balloon injury. Blockade of the selectins has a f avorable effect on the response to vascular injury.