Effect of glycosaminoglycans on thrombin- and atroxin-induced fibrin assembly and structure.
This study was performed to quantitate the impact of several glycosaminoglycans (GAG) on fibrin assembly and structure. Gel formation was monitored as the increase in optical density at 633 nm subsequent to thrombin (2 NIH u/ml) or atroxin (0.10 mg/ml) addition to solutions of buffered fibrinogen (1 mg/ml) or plasma. Gel absorbance was measured as a function of wavelength (400 to 800 nm) and gel fiber diameter and mass/length ratio (mu) were calculated. Chondroitin sulfate A (CSA) shortened the lag phase, enhanced the maximal rate of turbidity increase, and increased the final gel turbidity of fibrin gels formed by thrombin or atroxin. CSA (16 mg/ml) increased fiber mu from 1.3 to 3.1 x 10(13) dalton/cm and fiber radius from 6.0 to 8.6 x 10(-6) cm in thrombin-induced gels. Mu increased from 0.7 to 2.7 x 10(13) dalton/cm and fiber radius from 4 to 7.8 x 10(-6) cm for atroxin-induced gels. Above 16 mg/ml, CSA caused fibrinogen precipitation in purified solutions but not in plasma. CSA inhibited thrombin-induced plasma clotting of plasma but effects in atroxin-mediated plasma gels paralleled those seen in purified solutions. Chondroitin sulfate B (CSB)-induced changes in fibrin were similar but slightly less dramatic than those seen with CSA. Mu increased from 0.9 to 2.0 x 10(13) dalton/cm for atroxin-induced fibrin gels and from 0.8 to 2.3 x 10(13) dalton/cm for atroxin-induced gels. Low molecular weight heparin (Mr = 5100) slowed fibrin assembly and reduced fiber size by 50% in thrombin-induced gels. Changes in mu of atroxin-induced gels were much less pronounced (less than 20%).(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Medicine, Medical College of Virginia, Richmond.
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D012103:Batroxobin / Q000494:pharmacology; D001704:Biopolymers; D001777:Blood Coagulation / Q000502:physiology*; D002809:Chondroitin Sulfates / Q000502:physiology; D003871:Dermatan Sulfate / Q000502:physiology; D005337:Fibrin / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000502:physiology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009391:Nephelometry and Turbidimetry; D013917:Thrombin / Q000502:physiology
D012103:Batroxobin; D001704:Biopolymers; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D005337:Fibrin; D006025:Glycosaminoglycans; D006495:Heparin, Low-Molecular-Weight; D006497:Heparan Sulfate; D013917:Thrombin