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Nucleic acid scavengers inhibit thrombosis without increasing bleeding.

Publication ,  Journal Article
Jain, S; Pitoc, GA; Holl, EK; Zhang, Y; Borst, L; Leong, KW; Lee, J; Sullenger, BA
Published in: Proc Natl Acad Sci U S A
August 7, 2012

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 7, 2012

Volume

109

Issue

32

Start / End Page

12938 / 12943

Location

United States

Related Subject Headings

  • Thrombosis
  • Thrombelastography
  • Pulmonary Embolism
  • Polyphosphates
  • Nucleic Acids
  • Mice
  • Fibrinolytic Agents
  • Carotid Artery Injuries
  • Calorimetry
  • Blood Coagulation
 

Citation

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Jain, S., Pitoc, G. A., Holl, E. K., Zhang, Y., Borst, L., Leong, K. W., … Sullenger, B. A. (2012). Nucleic acid scavengers inhibit thrombosis without increasing bleeding. Proc Natl Acad Sci U S A, 109(32), 12938–12943. https://doi.org/10.1073/pnas.1204928109
Jain, Shashank, George A. Pitoc, Eda K. Holl, Ying Zhang, Luke Borst, Kam W. Leong, Jaewoo Lee, and Bruce A. Sullenger. “Nucleic acid scavengers inhibit thrombosis without increasing bleeding.Proc Natl Acad Sci U S A 109, no. 32 (August 7, 2012): 12938–43. https://doi.org/10.1073/pnas.1204928109.
Jain S, Pitoc GA, Holl EK, Zhang Y, Borst L, Leong KW, et al. Nucleic acid scavengers inhibit thrombosis without increasing bleeding. Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):12938–43.
Jain, Shashank, et al. “Nucleic acid scavengers inhibit thrombosis without increasing bleeding.Proc Natl Acad Sci U S A, vol. 109, no. 32, Aug. 2012, pp. 12938–43. Pubmed, doi:10.1073/pnas.1204928109.
Jain S, Pitoc GA, Holl EK, Zhang Y, Borst L, Leong KW, Lee J, Sullenger BA. Nucleic acid scavengers inhibit thrombosis without increasing bleeding. Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):12938–12943.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 7, 2012

Volume

109

Issue

32

Start / End Page

12938 / 12943

Location

United States

Related Subject Headings

  • Thrombosis
  • Thrombelastography
  • Pulmonary Embolism
  • Polyphosphates
  • Nucleic Acids
  • Mice
  • Fibrinolytic Agents
  • Carotid Artery Injuries
  • Calorimetry
  • Blood Coagulation