Heparin increased cell membrane-associated heparan sulfate proteoglycan in balloon-injured rat carotid artery.
The effect of heparin on the amount of membrane-associated heparan sulfate proteoglycan (HSPG) was examined biochemically in balloon-injured rat carotid arteries. Heparin (Choay 1772) was administered at the rate of 1 mg/kg/h.i.v. by an osmotic infusion pump for 10 days. Arterial tissues were incubated ex vivo with Na2(35)SO4 and 3H-glucosamine for 6 or 24 h. The arteries from heparin-treated rats were also incubated with heparin (100 micrograms/ml) during the radiolabeling. Membrane-associated proteoglycans were extracted with 4 M guanidine-HCl and isolated by a series of chromatographic steps using Sephadex G-50, DEAE-Sephacel and Octyl-Sepharose CL-4B. Membrane-associated proteoglycans were eluted with 0.8% Triton X-100 from Octyl-Sepharose columns. Heparin treatment significantly increased membrane-associated HSPG by 64% in the arteries incubated for 24 h, while heparin hardly increased the HSPG in 6 h incubated arteries. Since the 24-hour data seem to reflect a combination of biosynthesis and degradation of proteoglycans while the 6-hour data primarily reflect biosynthesis, these results suggest that inhibition of degradation of membrane-associated HSPG is involved in the mechanism of heparin action. This speculation is supported by the observation that membrane-associated HSPG was elevated in balloon-injured arteries by treatment with protease inhibitors.
Mutoh
S
S
Department of Surgery, School of Medicine, University of Washington, Seattle.
Clowes
M M
MM
Clowes
A W
AW
D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism*; D020212:Carotid Artery Injuries; D002404:Catheterization; D002462:Cell Membrane / Q000378:metabolism; D002847:Chromatography, Agarose; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D011480:Protease Inhibitors; D011509:Proteoglycans