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.
IBEX Technologies, Malvern, PA 19355, USA.
P J
PJ
Silver
J P
JP
Moreau
E
E
Denholm
Y Q
YQ
Lin
L
L
Nguyen
C
C
Bennett
A
A
Recktenwald
D
D
DeBlois
S
S
Baker
S
S
Ranger
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