Document Detail


Nucleic acid scavengers inhibit thrombosis without increasing bleeding.
MedLine Citation:
PMID:  22837404     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Development of effective, yet safe, antithrombotic agents has been challenging because such agents increase the propensity of patients to bleed. Recently, naturally occurring polyphosphates such as extracellular DNA, RNA, and inorganic polyphosphates have been shown to activate blood coagulation. In this report, we evaluate the anticoagulant and antithrombotic activity of nucleic acid-binding polymers in vitro and in vivo. Such polymers bind to DNA, RNA, and inorganic polyphosphate molecules with high affinity and inhibit RNA- and polyphosphate-induced clotting and the activation of the intrinsic pathway of coagulation in vitro. Moreover, [NH(2)(CH(2))(2)NH(2)](G = 3);dendri PAMAM(NH(2))(32) (PAMAM G-3) prevents thrombosis following carotid artery injury and pulmonary thromboembolism in mice without significantly increasing blood loss from surgically challenged animals. These studies indicate that nucleic acid-binding polymers are able to scavenge effectively prothrombotic nucleic acids and other polyphosphates in vivo and represent a new and potentially safer class of antithrombotic agents.
Authors:
Shashank Jain; George A Pitoc; Eda K Holl; Ying Zhang; Luke Borst; Kam W Leong; Jaewoo Lee; Bruce A Sullenger
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-25
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-08     Completed Date:  2012-10-15     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12938-43     Citation Subset:  IM    
Affiliation:
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Coagulation / drug effects*
Calorimetry
Carotid Artery Injuries / drug therapy
Fibrinolytic Agents / pharmacology*
Mice
Nucleic Acids / metabolism*
Polyphosphates / pharmacology*
Pulmonary Embolism / drug therapy
Thrombelastography
Thrombosis / drug therapy*
Grant Support
ID/Acronym/Agency:
HL065222/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibrinolytic Agents; 0/Nucleic Acids; 0/Polyphosphates
Comments/Corrections

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