title: Correlation between progressive adsorption of plasminogen to blood clots and their sensitivity to lysis.
abstract: The binding of plasminogen to preformed human plasma clots immersed in citrated human plasma was measured and correlated with the sensitivity of these clots to lysis with recombinant tissue-type plasminogen activator (rt-PA), recombinant single-chain urokinase-type plasminogen activator (rscu-PA) or two chain urokinase-type plasminogen activator (tcu-PA, urokinase). When 0.15 ml plasma clots were compressed mechanically to about 1% of their original weight, and immersed in 0.15 ml plasma, 131I-labeled native plasminogen (Glu-plasminogen) adsorbed progressively from the plasma milieu onto the clot; binding was 3 +/- 1% (n = 10) after 1 h, 7 +/- 1% after 12 h and 12 +/- 1% after 48 h. This was associated with an increased sensitivity of the clot to lysis; 50% clot lysis in 4 h was obtained with 65 +/- 5 ng/ml (n = 3) rt-PA before and 30 +/- 5 ng/ml (n = 3) after 48 h preincubation in plasma (p less than 0.01), with corresponding values of 660 +/- 55 ng/ml (n = 3) and 280 +/- 25 ng/ml (n = 3) for rscu-PA, (p less than 0.01), and 800 +/- 85 ng/ml (n = 3) and 270 +/- 35 ng/ml (n = 3) for urokinase (p less than 0.01). Additional binding of plasminogen and increased sensitivity to lysis were reduced or abolished when the clot was preincubated in plasminogen-depleted or in t-PA-depleted plasma, or when 20 mM 6-aminohexanoic acid or 2,000 KIU/ml aprotinin were added.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Sabovic
authors.forename: H R
authors.initials: HR
authors.lastname: Lijnen
authors.forename: D
authors.initials: D
authors.lastname: Keber
authors.forename: D
authors.initials: D
authors.lastname: Collen
mesh_terms: D000327:Adsorption; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood*
chemical_list: D005337:Fibrin; D010958:Plasminogen; D010960:Plasminogen Activators