EFFECT OF SHORT-TERM TREATMENT WITH A MONOCLONAL-ANTIBODY TO P-SELECTIN ON BALLOON CATHETER-INDUCED - INTIMAL HYPERPLASIA, RE-ENDOTHELIALIZATION, AND ATTENUATION OF ENDOTHELIAL-DEPENDENT RELAXATION

The effects of an anti-P-selectin monoclonal antibody (MAb, PB1.3; Cyt el Corporation) on neoendothelialization; neoendothelial function, as evidenced by acetylcholine-induced relaxation (nitric oxide formation) ; and intimal hyperplasia following embolectomy catheter-induced injur y to the rabbit thoracic aorta were investigated. Catheter injury was induced in two groups of New Zealand White rabbits. One group received no treatment, while the second group received short-term treatment wi th the MAb (i.p., immediately before and 12 h after induction of cathe ter injury), A third group underwent a sham operation and served as un injured controls. Following sacrifice at 2 weeks after injury, aortic rings were assessed for degree of intimal hyperplasia, neoendothelial morphology (scanning electron microscopy), and acetylcholine-induced r elaxation. Aortic tissue from catheter-injured animals that received t reatment exhibited improved neoendothelial morphology, as compared wit h tissue from untreated but catheterized animals; however, no statisti cally significant attenuation of the hyperplastic response or improvem ent in the attenuated neoendothelial-dependent acetylcholine-induced r elaxant response that is characteristic of neoendothelium that forms a fter catheter denudation was observed. These data suggest that short t erm attenuation of P-selectin-mediated poly morphonuclear leukocyte (P MN)endothelium, PMN/platelet interactions, and/or thrombin formation b eneficially affects neoendothelialization of the vascular wall followi ng balloon catheter-induced injury.