ROLE OF HYALURONATE IN THE ARTERIAL RESPONSE TO ANGIOPLASTY

Angioplasty has become enormously popular since its introduction in 19 79 for the treatment of arterial stenosis at coronary or other sites. The success rate is currently around 95%. Unfortunately, restenosis oc curs in 30 to 40% of cases within six months of the procedure. Resteno sis is the result of a number of events that are triggered by the angi oplasty. These events involve both blood components (platelets, leukoc ytes, and plasma constituents) and arterial wall components (smooth mu scle cells [SMCs], endothelial cells, and the extracellular matrix). H yaluronate is a high-molecular-weight glycosaminoglycane found in the extracellular matrix of arterial SMCs and endothelial cells. Hyalurona te and its receptors (CD44 and RHAMM or receptor for HA-mediated motil ity) contribute actively to leukocyte adhesion and infiltration at exp erimental angioplasty sites. Studies of cell cultures have shown that leukocyte adhesion and migration are inhibited by substances (antibodi es, peptides, high levels of hyaluronate) that prevent hyaluronate fro m binding to CD44 and RHAMM. Hyaluronate expression by arterial SMCs i s modulated by the angioplasty-produced arterial lesion. The SMCs that migrate and divide actively at the arterial lesion site are those tha t express hyaluronate, CD44, and RHAMM. Hyaluronate both stimulates SM C migration via an effect on RHAMM and enhances SMC division via an ef fect on CD44. In animal studies, administration of high levels of hyal uronate to saturate hyaluronate receptors on leukocytes and SMCs was f ollowed by inhibition of leukocyte infiltration into the damaged arter ial wall and by a significant reduction in the arterial neointima. Hya luronate, a compound with an excellent safety profile, may offer hope for the prevention of restenosis after angioplasty.