A novel human microplasmin fold: new perspective to thrombosis treatment.
The purpose of the present study was to obtain polypeptide chains with more specific fibrinolytic activity from normal human plasma. The isolation procedure was carried out in the presence of acetic acid and sodium borate (pH 9.9) purified with affinity and ionic interchange chromatography. Activity of microplasmin studied in vitro shows that the fibrin plate was used to measure the fibrinolytic activity. Rabbit thrombosis model was used to probe in-vivo fibrinolytic effects. Out of 13 male and female rabbits, seven (group A) were treated with microplasmin and six (group B) as placebo, weighing 2500-3200 g. Comparison of groups was made by analysis of variance with a statistical significance of 0.05%. In-vitro assay lysis (25 IU) was produced by microplasmin and tissue plasminogen activator. The fibrinolytic activity in rabbits showed 100% (7/7) reperfusion with microplasmin and 0% (0/7) with placebo (P = 0.002). The proposed scheme in this research for the fibrinolytic activity of microplasmin obtained by autolysis cleavage at new specific sites Lys-97-Val-98 and Ser-364-Thr-365 in the plasminogen involved in-vitro and in-vivo assays as a new specific fibrinolytic activity without haemorrhagic events. This microplasmin is different to the others and with more specific fibrinolysis.
Biological Chemistry Department, Chemistry Science Faculty, Medicine Faculty, Córdoba Catholic University, Córdoba, Argentina. ajoison2001@yahoo.com.ar
Agustín N
AN
Joison
Federico S
FS
Gallo
D000818:Animals; D005260:Female; D005341:Fibrinolysin / Q000302:isolation & purification / Q000627:therapeutic use*; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000302:isolation & purification / Q000627:therapeutic use*; D011817:Rabbits; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000188:drug therapy*
D005343:Fibrinolytic Agents; D010446:Peptide Fragments; C054561:microplasmin; D005341:Fibrinolysin