title: Nucleic acid scavengers inhibit thrombosis without increasing bleeding.
abstract: 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: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors: Shashank
authors: S
authors: Jain
authors: George A
authors: GA
authors: Pitoc
authors: Eda K
authors: EK
authors: Holl
authors: Ying
authors: Y
authors: Zhang
authors: Luke
authors: L
authors: Borst
authors: Kam W
authors: KW
authors: Leong
authors: Jaewoo
authors: J
authors: Lee
authors: Bruce A
authors: BA
authors: Sullenger
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002151:Calorimetry; D020212:Carotid Artery Injuries / Q000188:drug therapy; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D051379:Mice; D009696:Nucleic Acids / Q000378:metabolism*; D011122:Polyphosphates / Q000494:pharmacology*; D011655:Pulmonary Embolism / Q000188:drug therapy; D013916:Thrombelastography; D013927:Thrombosis / Q000188:drug therapy*
chemical_list: D005343:Fibrinolytic Agents; D009696:Nucleic Acids; D011122:Polyphosphates