A bi-functional anti-thrombosis protein containing both direct-acting fibrin(ogen)olytic and plasminogen-activating activities.

Abstract

UNLABELLED:

Direct-acting fibrin(ogen)olytic agents such as plasmin have been proved to contain effective and safety thrombolytic potential. Unfortunately, plasmin is ineffective when administered by the intravenous route because it was neutralized by plasma antiplasmin. Direct-acting fibrin(ogen)olytic agents with resistance against antiplasmin will brighten the prospect of anti-thrombosis. As reported in 'Compendium of Materia Medica', the insect of Eupolyphaga sinensis Walker has been used as traditional anti-thrombosis medicine without bleeding risk for several hundreds years. Currently, we have identified a fibrin(ogen)olytic protein (Eupolytin1) containing both fibrin(ogen)olytic and plasminogen-activating (PA) activities from the beetle, E. sinensis.

OBJECTIVES:

To investigate the role of native and recombinant eupolytin1 in fibrin(ogen)olytic and plasminogen-activating processes.

METHODS AND RESULTS:

Using thrombus animal model, eupolytin1 was proved to contain strong and rapid thrombolytic ability and safety in vivo, which are better than that of urokinase. Most importantly, no bleeding complications were appeared even the intravenous dose up to 0.12 µmol/kg body weight (3 times of tested dose which could completely lyse experimental thrombi) in rabbits. It is the first report of thrombolytic agents containing both direct-acting fibrin(ogen)olytic and plasminogen-activating activities.

CONCLUSIONS:

The study identified novel thrombolytic agent with prospecting clinical potential because of its bi-functional merits containing both plasmin- and PA-like activities and unique pharmacological kinetics in vivo.

• Authors: Hailong Yang, Yipeng Wang, Yao Xiao, Ying Wang, Jing Wu, Cunbao Liu, Huahu Ye, Fengliang Li, Haining Yu, Ren Lai
• Journal: PloS one (PLoS One) Vol. 6 Issue 3 Pg. e17519 (Mar 14 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21423730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antithrombin Proteins
• Plasminogen Activators
• Urokinase-Type Plasminogen Activator

Topics

• Amino Acid Sequence
• Animals
• Antithrombin Proteins (administration & dosage, chemistry, isolation & purification, metabolism)
• Bleeding Time
• Coleoptera
• Fibrinolysis (drug effects)
• Gastrointestinal Tract (metabolism)
• Hemostasis (drug effects)
• Humans
• Hydrolysis (drug effects)
• Kinetics
• Mice
• Molecular Sequence Data
• Phylogeny
• Plasminogen Activators (metabolism)
• Rabbits
• Urokinase-Type Plasminogen Activator (pharmacology)