Document Detail


Nitrophorin 2, a factor IX(a)-directed anticoagulant, inhibits arterial thrombosis without impairing haemostasis.
MedLine Citation:
PMID:  20838739     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nitrophorin 2 (NP2) is a 20 kDa lipocalin identified in the salivary gland of the blood sucking insect, Rhodnius prolixus. It functions as a potent inhibitor of the intrinsic pathway of coagulation upon binding to factor IX (FIX) or FIXa. Herein we have investigated the in vivo antithrombotic properties of NP2. Surface plasmon resonance assays demonstrated that NP2 binds to rat FIX and FIXa with high affinities (KD = 43 and 47 nM, respectively), and prolongs the aPTT without affecting the PT. In order to evaluate NP2 antithrombotic effects in vivo two distinct models of thrombosis in rats were carried out. In the rose Bengal/laser induced injury model of arterial thrombosis, NP2 increased the carotid artery occlusion time by ≍35 and ≍155%, at doses of 8 and 80 μg/kg, respectively. NP2 also inhibited thrombus formation in an arterio-venous shunt model, showing ≍60% reduction at 400 μg/kg (i.v. administration). The antithrombotic effect lasted for up to 48 hours after a single i.v. dose. Notably, effective doses of NP2 did not increase the blood loss as evaluated by tail-transection model. In conclusion, NP2 is a potent and long-lasting inhibitor of arterial thrombosis with minor effects on haemostasis. It might be regarded as a potential agent for the treatment of human cardiovascular diseases.
Authors:
Daniella M Mizurini; Ivo M B Francischetti; John F Andersen; Robson Q Monteiro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-13
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  104     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-02     Completed Date:  2011-03-24     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1116-23     Citation Subset:  IM    
Affiliation:
Instituto de Bioquímica Médica/CCS/UFRJ, Avenida Carlos Chagas Filho 373, Cidade Universitária, Ilha do Fundão, Rio de Janeiro 21941590, Brazil.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticoagulants / administration & dosage,  metabolism,  pharmacology*
Disease Models, Animal
Factor IXa / antagonists & inhibitors*,  metabolism
Female
Fibrinolytic Agents / administration & dosage,  metabolism,  pharmacology*
Hemeproteins / administration & dosage,  metabolism,  pharmacology*
Hemostasis / drug effects*
Injections, Intravenous
Kinetics
Male
Partial Thromboplastin Time
Protein Binding
Prothrombin Time
Rats
Rats, Wistar
Salivary Proteins and Peptides / administration & dosage,  metabolism,  pharmacology*
Surface Plasmon Resonance
Thrombin / metabolism
Thrombosis / blood,  etiology,  prevention & control*
Grant Support
ID/Acronym/Agency:
Z01 AI000810-11/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Fibrinolytic Agents; 0/Hemeproteins; 0/Salivary Proteins and Peptides; 0/nitrophorin; EC 3.4.21.22/Factor IXa; EC 3.4.21.5/Thrombin
Comments/Corrections

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