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.