Ecotin: Exploring a feasible antithrombotic profile.

Abstract

Ecotin is an Escherichia coli-derived protein that can inhibit serine proteases. It has been suggested that this protein (ecotin-WT) and some of its variants could be used to develop a prototype to treat thrombosis. In this work, the effect of ecotin-WT and a variant of this protein harboring two mutations (Met84Arg and Met85Arg, ecotin-RR) were analyzed to determine their ability to prevent thrombus formation using in vivo models. Ecotins were analyzed in vitro using the coagulation tests. An in vivo venous thrombosis rat model and a pulmonary thromboembolism mouse model were used to investigate the antithrombotic activity. The bleeding time in rats using a tail-transection model was evaluated as a possible side effect caused by the administration of these proteins. Ecotin-RR was more effective in inhibiting thrombin than ecotin-WT. Both ecotins presented similar mechanisms of anticoagulation activity and were able to decrease thrombus formation. In contrast, only ecotin-RR increased survival rates in the in vivo pulmonary thromboembolism model, reinforcing the antithrombotic activity of ecotin-RR. Ecotin-WT and more so ecotin-RR showed potent antithrombotic effects, not associated with bleeding. The presented results indicate that ecotin-WT and ecotin-RR may be new scaffolds that could be used to develop anticoagulation molecules.

• Authors: Luciana Serrão Wermelinger, Flávia Serra Frattani, Tatiana Correa Carneiro-Lobo, Charles S Craik, Helena Carla Castro, Russolina Benedeta Zingali
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 78 Pg. 296-303 (Jul 2015) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 25881959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Anticoagulants
• Eco protein, E coli
• Escherichia coli Proteins
• Fibrinolytic Agents
• Periplasmic Proteins
• Serine Proteases

Topics

• Animals
• Anticoagulants (chemistry, pharmacology)
• Disease Models, Animal
• Enzyme Activation
• Escherichia coli Proteins (chemistry, pharmacology)
• Female
• Fibrinolytic Agents (chemistry, pharmacology)
• Hemorrhage (drug therapy)
• Humans
• Male
• Mice
• Periplasmic Proteins (chemistry, pharmacology)
• Rats
• Serine Proteases (metabolism)
• Thromboembolism (blood, drug therapy)