HEPARINASE-III LIMITS RAT ARTERIAL SMOOTH-MUSCLE CELL-PROLIFERATION IN-VITRO AND IN-VIVO

Heparinase III degrades heparan sulfate proteoglycans, which are co-re ceptors for growth factors that stimulate arterial proliferation. We a ssessed the ability of locally-delivered heparinase III to limit media l vascular smooth muscle cell proliferation induced by balloon cathete r injury in rat carotid arteries. Whereas vehicle-treated arteries sho wed 12% of smooth muscle cells proliferating after 2 days, heparinase III (0.022-5.7 mg/kg) treated arteries showed 0.8-4%. Chemically-inact ivated heparinase III did not limit proliferation. in isolated rat A10 vascular smooth muscle cells, heparinase III (1 IU/ml) inhibited both PDGF-BB and bFGF mediated increases in proliferation and migration. T hese results suggest that heparinase III can limit proliferation by af fecting heparan sulfate proteoglycan binding growth factors following arterial injury. (C) 1998 Elsevier Science B.V. All rights reserved.