Literature DB >> 25065530

Probing the coagulation pathway with aptamers identifies combinations that synergistically inhibit blood clot formation.

Kristin M Bompiani1, Jens L Lohrmann2, George A Pitoc2, James W Frederiksen2, George B Mackensen3, Bruce A Sullenger4.   

Abstract

Coordinated enzymatic reactions regulate blood clot generation. To explore the contributions of various coagulation enzymes in this process, we utilized a panel of aptamers against factors VIIa, IXa, Xa, and prothrombin. Each aptamer dose-dependently inhibited clot formation, yet none was able to completely impede this process in highly procoagulant settings. However, several combinations of two aptamers synergistically impaired clot formation. One extremely potent aptamer combination was able to maintain human blood fluidity even during extracorporeal circulation, a highly procoagulant setting encountered during cardiopulmonary bypass surgery. Moreover, this aptamer cocktail could be rapidly reversed with antidotes to restore normal hemostasis, indicating that even highly potent aptamer combinations can be rapidly controlled. These studies highlight the potential utility of using sets of aptamers to probe the functions of proteins in molecular pathways for research and therapeutic ends.
Copyright © 2014 Elsevier Ltd. All rights reserved.

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Year:  2014        PMID: 25065530      PMCID: PMC4134678          DOI: 10.1016/j.chembiol.2014.05.016

Source DB:  PubMed          Journal:  Chem Biol        ISSN: 1074-5521


  38 in total

Review 1.  The heparin-protamine interaction. A review.

Authors:  J A Carr; N Silverman
Journal:  J Cardiovasc Surg (Torino)       Date:  1999-10       Impact factor: 1.888

Review 2.  Heparin-induced thrombocytopenia: a clinicopathologic syndrome.

Authors:  T E Warkentin
Journal:  Thromb Haemost       Date:  1999-08       Impact factor: 5.249

Review 3.  Platelets and thrombin generation.

Authors:  Dougald M Monroe; Maureane Hoffman; Harold R Roberts
Journal:  Arterioscler Thromb Vasc Biol       Date:  2002-09-01       Impact factor: 8.311

4.  Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR pharmacokinetic and pharmacodynamic substudy.

Authors:  Thomas J Povsic; William A Wargin; John H Alexander; Joshua Krasnow; Merill Krolick; Mauricio G Cohen; Roxana Mehran; Christopher E Buller; Christoph Bode; Steven L Zelenkofske; Christopher P Rusconi; Richard C Becker
Journal:  Eur Heart J       Date:  2011-06-30       Impact factor: 29.983

5.  Potent anticoagulant aptamer directed against factor IXa blocks macromolecular substrate interaction.

Authors:  Bruce Sullenger; Rebecca Woodruff; Dougald M Monroe
Journal:  J Biol Chem       Date:  2012-02-13       Impact factor: 5.157

6.  A high affinity, antidote-controllable prothrombin and thrombin-binding RNA aptamer inhibits thrombin generation and thrombin activity.

Authors:  K M Bompiani; D M Monroe; F C Church; B A Sullenger
Journal:  J Thromb Haemost       Date:  2012-05       Impact factor: 5.824

7.  An anticoagulant RNA aptamer that inhibits proteinase-cofactor interactions within prothrombinase.

Authors:  Sai K Buddai; Juliana M Layzer; Genmin Lu; Christopher P Rusconi; Bruce A Sullenger; Dougald M Monroe; Sriram Krishnaswamy
Journal:  J Biol Chem       Date:  2009-12-18       Impact factor: 5.157

8.  First clinical application of an actively reversible direct factor IXa inhibitor as an anticoagulation strategy in patients undergoing percutaneous coronary intervention.

Authors:  Mauricio G Cohen; Drew A Purdy; Joseph S Rossi; Liliana R Grinfeld; Shelley K Myles; Laura H Aberle; Adam B Greenbaum; Edward Fry; Mark Y Chan; Ross M Tonkens; Steven Zelenkofske; John H Alexander; Robert A Harrington; Christopher P Rusconi; Richard C Becker
Journal:  Circulation       Date:  2010-07-26       Impact factor: 29.690

9.  Heparin and calcium ions dramatically enhance antithrombin reactivity with factor IXa by generating new interaction exosites.

Authors:  Tina Bedsted; Richard Swanson; Yung-Jen Chuang; Paul E Bock; Ingemar Björk; Steven T Olson
Journal:  Biochemistry       Date:  2003-07-15       Impact factor: 3.162

10.  RNA aptamers as reversible antagonists of coagulation factor IXa.

Authors:  Christopher P Rusconi; Elizabeth Scardino; Juliana Layzer; George A Pitoc; Thomas L Ortel; Dougald Monroe; Bruce A Sullenger
Journal:  Nature       Date:  2002-09-05       Impact factor: 49.962

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  4 in total

1.  Targeting Two Coagulation Cascade Proteases with a Bivalent Aptamer Yields a Potent and Antidote-Controllable Anticoagulant.

Authors:  Erin E Soule; Kristin M Bompiani; Rebecca S Woodruff; Bruce A Sullenger
Journal:  Nucleic Acid Ther       Date:  2015-11-19       Impact factor: 5.486

Review 2.  Aptamers as targeted therapeutics: current potential and challenges.

Authors:  Jiehua Zhou; John Rossi
Journal:  Nat Rev Drug Discov       Date:  2016-11-03       Impact factor: 84.694

3.  Combining Heparin and a FX/Xa Aptamer to Reduce Thrombin Generation in Cardiopulmonary Bypass and COVID-19.

Authors:  Charlene V Chabata; James W Frederiksen; Lyra B Olson; Ibtehaj A Naqvi; Sharon E Hall; Ruwan Gunaratne; Bryan D Kraft; Loretta G Que; Lingye Chen; Bruce A Sullenger
Journal:  Nucleic Acid Ther       Date:  2022-01-12       Impact factor: 4.244

4.  Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass.

Authors:  Ruwan Gunaratne; Shekhar Kumar; James W Frederiksen; Steven Stayrook; Jens L Lohrmann; Kay Perry; Kristin M Bompiani; Charlene V Chabata; Nabil K Thalji; Michelle D Ho; Gowthami Arepally; Rodney M Camire; Sriram Krishnaswamy; Bruce A Sullenger
Journal:  Nat Biotechnol       Date:  2018-06-04       Impact factor: 54.908

  4 in total

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