Suppression of arterial thrombosis without affecting hemostatic parameters with a cell-penetrating PAR1 pepducin

Circulation

Volumn 126, Issue 1, 2012, Pages 83-91

  Zhang, Ping ^a   Gruber, András ^d,e   Kasuda, Shogo ^a   Kimmelstiel, Carey ^b,c   O'Callaghan, Katie ^a   Cox, Daniel H ^c   Bohm, Andrew ^c   Baleja, James D ^c   Covic, Lidija ^a,c   Kuliopulos, Athan ^a,c  

^a TUFTS MEDICAL CENTER   (United States)

^b Division of Cardiology   (United States)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e Oregon Health and Science University Department of Biomedical Engineering   (United States)

Author keywords

Antiplatelet therapy; Drug delivery system; PAR1; Platelets; Thrombosis

Indexed keywords

CLOPIDOGREL; PAR1 PROTEIN; PZ 128; THROMBIN RECEPTOR; THROMBIN RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ACUTE CORONARY SYNDROME; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICOAGULATION; ARTERY THROMBOSIS; ARTICLE; BLEEDING; BLOOD CLOT LYSIS; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG SYNTHESIS; DRUG TARGETING; FEMALE; MALE; NONHUMAN; PERCUTANEOUS CORONARY INTERVENTION; PRIORITY JOURNAL; THROMBOCYTE AGGREGATION INHIBITION; THROMBOCYTE FUNCTION;

ANIMALS; CELL MEMBRANE; GUINEA PIGS; HEMOSTASIS; HUMANS; LIPOPEPTIDES; MACACA FASCICULARIS; MALE; PAPIO ANUBIS; PLATELET ACTIVATION; PLATELET AGGREGATION INHIBITORS; RECEPTOR, PAR-1; THROMBOSIS;

EID: 84863622714     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.112.091918     Document Type: Article

References (45)

1. Gurbel PA, Bliden KP, Saucedo JF, Suarez TA, DiChiara J, Antonino MJ, Mahla E, Singla A, Herzog WR, Bassi AK, Hennebry TA, Gesheff TB, Tantry US. Bivalirudin and clopidogrel with and without eptifibatide for elective stenting: effects on platelet function, thrombelastographic indexes, and their relation to periprocedural infarction results of the CLEAR PLATELETS-2 (Clopidogrel with Eptifibatide to Arrest the Reactivity of Platelets) study. J Am Coll Cardiol. 2009;53:648-657.
2. Lansky AJ, Stone GW. Periprocedural myocardial infarction: prevalence, prognosis, and prevention. Circ Cardiovasc Interv. 2010;3:602-610.
3. Brar SS, ten Berg J, Marcucci R, Price MJ, Valgimigli M, Kim HS, Patti G, Breet NJ, DiSciascio G, Cuisset T, Dangas G. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol. 2011;58:1945-1954.
4. Coller BS. Historical perspective and future directions in platelet research. J Thromb Haemost. 2011;9(SUPPL. 1):374-395.
5. Smyth SS, Woulfe DS, Weitz JI, Gachet C, Conley PB, Goodman SG, Roe MT, Kuliopulos A, Moliterno DJ, French PA, Steinhubl SR, Becker RC. G-protein-coupled receptors as signaling targets for antiplatelet therapy. Arterioscler Thromb Vasc Biol. 2009;29:449-457.
6. Jackson SP, Nesbitt WS, Kulkarni S. Signaling events underlying thrombus formation. J Thromb Haemost. 2003;1:1602-1612.
7. Steinhubl SR, Schneider DJ, Berger PB, Becker RC. Determining the efficacy of antiplatelet therapies for the individual: lessons from clinical trials. J Thromb Thrombolysis. 2008;26:8-13.
8. Faxon DP, Freedman JE. Facts and controversies of aspirin and clopidogrel therapy. Am Heart J. 2009;157:412-422.
9. Gurbel PA, Tantry US. Combination antithrombotic therapies. Circulation. 2010;121:569-583.
10. Leger AJ, Covic L, Kuliopulos A. Protease-activated receptors and cardiovascular diseases. Circulation. 2006;113:1070-1077.
11. Antoniak S, Pawlinski R, Mackman N. Protease-activated receptors and myocardial infarction. IUBMB Life. 2011;63:383-389.
12. Tricoci P, Huang Z, Held C, Moliterno DJ, Armstrong PW, Van de Werf F, White HD, Aylward PE, Wallentin L, Chen E, Lokhnygina Y, Pei J, Leonardi S, Rorick TL, Kilian AM, Jennings LH, Ambrosio G, Bode C, Cequier A, Cornel JH, Diaz R, Erkan A, Huber K, Hudson MP, Jiang L, Jukema JW, Lewis BS, Lincoff AM, Montalescot G, Nicolau JC, Ogawa H, Pfisterer M, Prieto JC, Ruzyllo W, Sinnaeve PR, Storey RF, Valgimigli M, Whellan DJ, Widimsky P, Strony J, Harrington RA, Mahaffey KW. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;366:20-33.
13. Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Mary Polly Fish BA, Fox KAA, Lipka LJ, Liu X, Nicolau JC, Ophuis AJO, Paolasso E, Scirica BM, Spinar J, Theroux P, Wiviott SD, Strony J, Murphy SA, for the TRA 2P-TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366:1404-1413.
14. Leger AJ, Jacques SL, Badar J, Kaneider NC, Derian CK, Andrade-Gordon P, Covic L, Kuliopulos A. Blocking the protease-activated receptor 1-4 heterodimer in platelet-mediated thrombosis. Circulation. 2006;113:1244-1254.
15. Jacques S, LeMasurier M, Sheridan PJ, Seeley SK, Kuliopulos A. Substrate-assisted catalysis of the PAR1 thrombin receptor: enhancement of macromolecular association and cleavage. J Biol Chem. 2000;275: 40671-40678. (Pubitemid 32054883)
16. Jacques SL, Kuliopulos A. Protease-activated receptor-4 uses dual prolines and an anionic recognition motif for thrombin recognition and cleavage. Biochem J. 2003;376:733-740. (Pubitemid 38058072)
17. Covic L, Gresser AL, Kuliopulos A. Biphasic kinetics of activation and signaling for PAR1 and PAR4 thrombin receptors in platelets. Biochemistry. 2000;39:5458-5467. (Pubitemid 30257087)
18. Kimmelstiel C, Zhang P, Kapur NK, Weintraub A, Krishnamurthy B, Castaneda V, Covic L, Kuliopulos A. Bivalirudin is a dual inhibitor of thrombin and collagen-dependent platelet activation in patients undergoing percutaneous coronary intervention. Circ Cardiovasc Interv. 2011;4:171-179.
19. Covic L, Singh C, Smith H, Kuliopulos A. Role of the PAR4 thrombin receptor in stabilizing platelet-platelet aggregates as revealed by a patient with Hermansky-Pudlak syndrome. Thromb Haemost. 2002;87:722-727. (Pubitemid 34302962)
20. Becker RC, Moliterno DJ, Jennings LK, Pieper KS, Pei J, Niederman A, Ziada KM, Berman G, Strony J, Joseph D, Mahaffey KW, Van de Werf F, Veltri E, Harrington RA. Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study. Lancet. 2009;373:919-928.
21. Goto S, Yamaguchi T, Ikeda Y, Kato K, Yamaguchi H, Jensen P. Safety and exploratory efficacy of the novel thrombin receptor (PAR-1) antagonist SCH530348 for non-ST-segment elevation acute coronary syndrome. J Atheroscler Thromb. 2010;17:156-164.
22. Goto S, Ogawa H, Takeuchi M, Flather MD, Bhatt DL. Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease. Eur Heart J. 2010;31: 2601-2613.
23. O'Donoghue ML, Bhatt DL, Wiviott SD, Goodman SG, Fitzgerald DJ, Angiolillo DJ, Goto S, Montalescot G, Zeymer U, Aylward PE, Guetta V, Dudek D, Ziecina R, Contant CF, Flather MD. Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of Thrombin-Acute Coronary Syndromes Trial. Circulation. 2011;123:1843-1853.
24. Kosoglou T, Reyderman L, Tiessen RG, van Vliet AA, Fales RR, Keller R, Yang B, Cutler DL. Pharmacodynamics and pharmacokinetics of the novel PAR-1 antagonist vorapaxar (formerly SCH 530348) in healthy subjects. Eur J Clin Pharmacol. 2012;68:249-58.
25. Covic L, Gresser AL, Talavera J, Swift S, Kuliopulos A. Activation and inhibition of G protein-coupled receptors by cell-penetrating membranetethered peptides. Proc Natl Acad Sci U S A. 2002;99:643-648. (Pubitemid 34106565)
26. Covic L, Tchernychev B, Jacques S, Kuliopulos A. Pharmacology and in vivo efficacy of pepducins in hemostasis and arterial thrombosis. In: Langel U, ed. Handbook of Cell-Penetrating Peptides. 2nd ed. New York, NY: Taylor & Francis; 2007:245-257.
27. Covic L, Misra M, Badar J, Singh C, Kuliopulos A. Pepducin-based intervention of thrombin receptor signaling and systemic platelet activation. Nature Med. 2002;8:1161-1165. (Pubitemid 35175972)
28. Sevigny LM, Zhang P, Bohm A, Lazarides K, Perides G, Covic L, Kuliopulos A. Interdicting protease-activated receptor-2-driven inflammation with cell-penetrating pepducins. Proc Natl Acad Sci U S A. 2011; 108:8491-8496.
29. Kuliopulos A, Covic L. Blocking receptors on the inside: pepducin-based intervention of PAR signaling and thrombosis. Life Sc. 2003;74:255-262. (Pubitemid 37357056)
30. Liu Y, Liu Z, Androphy E, Chen J, Baleja JD. Design and characterization of helical peptides that inhibit the E6 protein of papillomavirus. Biochemistry. 2004;43:7421-7431. (Pubitemid 38745759)
31. Hanson SR, Kotze HF, Savage B, Harker LA. Platelet interactions with Dacron vascular grafts. A model of acute thrombosis in baboons. Arteriosclerosis. 1985;5:595-603.
32. Pinheiro JC, Bates DM. Mixed-effects Models in S and S-plus. New York, NY: Springer; 2000.
33. Wielders SJ, Bennaghmouch A, Reutelingsperger CP, Bevers EM, Lindhout T. Anticoagulant and antithrombotic properties of intracellular protease-activated receptor antagonists. J Thromb Haemost. 2007;5:571-576. (Pubitemid 46680691)
34. Scheerer P, Park JH, Hildebrand PW, Kim YJ, Krauss N, Choe HW, Hofmann KP, Ernst OP. Crystal structure of opsin in its G-proteininteracting conformation. Nature. 2008;455:497-502.
35. Trivedi V, Boire A, Tchernychev B, Kaneider NC, Leger AJ, O'Callaghan K, Covic L, Kuliopulos A. Platelet matrix metalloprotease-1 mediates thrombogenesis by activating PAR1 at a cryptic ligand site. Cell. 2009;137:332-343.
36. Eckly A, Hechler B, Freund M, Zerr M, Cazenave JP, Lanza F, Mangin PH, Gachet C. Mechanisms underlying FeCl3-induced arterial thrombosis. J Thromb Haemost. 2011;9:779-789.
37. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001-2015. (Pubitemid 350106708)
38. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, Freij A, Thorsen M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045-1057.
39. Roe MT, Ohman EM. A new era in secondary prevention after acute coronary syndrome. N Engl J Med. 2011;366:85-87.
40. Chintala M, Shimizu K, Ogawa M, Yamaguchi H, Doi M, Jensen P. Basic and translational research on proteinase-activated receptors: antagonism of the proteinase-activated receptor 1 for thrombin, a novel approach to antiplatelet therapy for atherothrombotic disease. J Pharmacol Sci. 2008; 108:433-438.
41. Derian CK, Damiano BP, Addo MF, Darrow AL, D'Andrea MR, Nedelman M, Zhang HC, Maryanoff BE, Andrade-Gordon P. Blockade of the thrombin receptor protease-activated receptor-1 with a smallmolecule antagonist prevents thrombus formation and vascular occlusion in nonhuman primates. J Pharmacol Exp Ther. 2003;304:855-861. (Pubitemid 36152366)
42. Kato Y, Kita Y, Hirasawa-Taniyama Y, Nishio M, Mihara K, Ito K, Yamanaka T, Seki J, Miyata S, Mutoh S. Inhibition of arterial thrombosis by a protease-activated receptor 1 antagonist, FR171113, in the guinea pig. Eur J Pharmacol. 2003;473:163-169. (Pubitemid 36929880)
43. Jennings LK. Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost. 2009;102:248-257.
44. Cisowski J, O'Callaghan K, Kuliopulos A, Yang J, Nguyen N, Deng Q, Yang E, Fogel M, Tressel S, Foley C, Agarwal A, Hunt SW 3rd, McMurry T, Brinckerhoff L, Covic L. Targeting protease-activated receptor-1 with cell-penetrating pepducins in lung cancer. Am J Pathol. 2011;179:513-523.
45. Dimond P, Carlson K, Bouvier M, Gerard C, Xu L, Covic L, Agarwal A, Ernst OP, Janz JM, Schwartz TW, Gardella TJ, Milligan G, Kuliopulos A, Sakmar TP, Hunt SW 3rd. G protein-coupled receptor modulation with pepducins: moving closer to the clinic. Ann N Y Acad Sci. 2011;1226:34-49.