Heparinase III limits rat arterial smooth muscle cell proliferation in vitro and in vivo.
Heparinase III degrades heparan sulfate proteoglycans, which are co-receptors for growth factors that stimulate arterial proliferation. We assessed the ability of locally-delivered heparinase III to limit medial vascular smooth muscle cell proliferation induced by balloon catheter injury in rat carotid arteries. Whereas vehicle-treated arteries showed 12% of smooth muscle cells proliferating after 2 days, heparinase III (0.022-5.7 mg/kg) treated arteries showed 0.8-4%. Chemically-inactivated 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. These results suggest that heparinase III can limit proliferation by affecting heparan sulfate proteoglycan binding growth factors following arterial injury.
Silver
P J
PJ
IBEX Technologies, Malvern, PA 19355, USA.
Moreau
J P
JP
Denholm
E
E
Lin
Y Q
YQ
Nguyen
L
L
Bennett
C
C
Recktenwald
A
A
DeBlois
D
D
Baker
S
S
Ranger
S
S
D000818:Animals; D000077214:Becaplermin; D002342:Carotid Artery, External / Q000187:drug effects* / Q000473:pathology; D016893:Carotid Stenosis / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D011133:Polysaccharide-Lyases / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley
D019812:Heparan Sulfate Proteoglycans; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase