[Role of hyaluronic acid in the arterial response to angioplasty].

Angioplasty has become enormously popular since its introduction in 1979 for the treatment of arterial stenosis at coronary or other sites. The success rate is currently around 95%. Unfortunately, restenosis occurs in 30 to 40% of cases within six months of the procedure. Restenosis is the result of a number of events that are triggered by the angioplasty. These events involve both blood components (platelets, leukocytes, and plasma constituents) and arterial wall components (smooth muscle cells [SMCs], endothelial cells, and the extracellular matrix). Hyaluronate is a high-molecular-weight glycosaminoglycane found in the extracellular matrix of arterial SMCs and endothelial cells. Hyaluronate and its receptors (CD44 and RHAMM or receptor for HA-mediated motility) contribute actively to leukocyte adhesion and infiltration at experimental angioplasty sites. Studies of cell cultures have shown that leukocyte adhesion and migration are inhibited by substances (antibodies, peptides, high levels of hyaluronate) that prevent hyaluronate from binding to CD44 and RHAMM. Hyaluronate expression by arterial SMCs is modulated by the angioplasty-produced arterial lesion. The SMCs that migrate and divide actively at the arterial lesion site are those that express hyaluronate, CD44, and RHAMM. Hyaluronate both stimulates SMC migration via an effect on RHAMM and enhances SMC division via an effect on CD44. In animal studies, administration of high levels of hyaluronate to saturate hyaluronate receptors on leukocytes and SMCs was followed by inhibition of leukocyte infiltration into the damaged arterial wall and by a significant reduction in the arterial neointima. Hyaluronate, a compound with an excellent safety profile, may offer hope for the prevention of restenosis after angioplasty.