Korean Circulation Journal

  • 제52권10호
  • /
  • Pages.737-754
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  • 2022
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  • 1738-5520(pISSN)
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  • 1738-5555(eISSN)
대한심장학회 (The Korean Society of Cardiology)
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Pharmacological Approaches to Limit Ischemic and Reperfusion Injuries of the Heart: Analysis of Experimental and Clinical Data on P2Y12 Receptor Antagonists

  • Leonid N. Maslov (Cardiology Research Institute, Tomsk National Research Medical Center of the RAS) ;
  • Sergey V. Popov (Cardiology Research Institute, Tomsk National Research Medical Center of the RAS) ;
  • Alexandr V. Mukhomedzyanov (Cardiology Research Institute, Tomsk National Research Medical Center of the RAS) ;
  • Ivan A. Derkachev (Cardiology Research Institute, Tomsk National Research Medical Center of the RAS) ;
  • Vyacheslav V. Ryabov (Cardiology Research Institute, Tomsk National Research Medical Center of the RAS) ;
  • Alla A. Boshchenko (Cardiology Research Institute, Tomsk National Research Medical Center of the RAS) ;
  • N. Rajendra Prasad (Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University) ;
  • Galina Z. Sufianova (Tyumen State Medical University) ;
  • Maria S. Khlestkina (Tyumen State Medical University) ;
  • Ilgiz Gareev (Tyumen State Medical University)
  • 투고 : 2022.06.02
  • 심사 : 2022.08.24
  • 발행 : 2022.10.01
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초록

Ischemic and reperfusion injuries of the heart underlie the pathogenesis of acute myocardial infarction (AMI) and sudden cardiac death. The mortality rate is still high and is 5-7% in patients with ST-segment elevation myocardial infarction. The review is devoted to pharmacological approaches to limitation of ischemic and reperfusion injuries of the heart. The article analyzes experimental evidence and the clinical data on the effects of P2Y12 receptor antagonists on the heart's tolerance to ischemia/reperfusion in animals with coronary artery occlusion and reperfusion and also in patients with AMI. Chronic administration of ticagrelor prevented adverse remodeling of the heart. There is evidence that sphingosine-1-phosphate is the molecule that mediates the infarct-reducing effect of P2Y12 receptor antagonists. It was discussed a role of adenosine in the cardioprotective effect of ticagrelor.

키워드

과제정보

This article was prepared with the support of Ministry of Science and High Education of RF a state assignment 122020300042-4.

참고문헌

  1. Fabris E, Kilic S, Schellings DAAM, et al. Long-term mortality and prehospital tirofiban treatment in patients with ST elevation myocardial infarction. Heart 2017;103:1515-20.
  2. Hinton J, Mariathas M, Gabara L, et al. Distribution of contemporary sensitivity troponin in the emergency department and relationship to 30-day mortality: The CHARIOT-ED substudy. Clin Med (Lond) 2020;20:528-34.
  3. Menees DS, Peterson ED, Wang Y, et al. Door-to-balloon time and mortality among patients undergoing primary PCI. N Engl J Med 2013;369:901-9.
  4. Olier I, Sirker A, Hildick-Smith DJR, et al. Association of different antiplatelet therapies with mortality after primary percutaneous coronary intervention. Heart 2018;104:1683-90.
  5. Gong X, Ding X, Chen H, Li H. Real-world use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/β-blocks in Chinese patients before acute myocardial infarction occurs: patient characteristics and hospital follow-up. J Transl Med 2018;16:346.
  6. Maslov LN, Barbarash OL. Pharmacological approaches to limiting the infarct zone size in patients with acute myocardial infarction: analysis of clinical data. Eksp Klin Farmakol 2018;81:34-41.
  7. Ndrepepa G. Improving myocardial injury, infarct size, and myocardial salvage in the era of primary PCI for STEMI. Coron Artery Dis 2015;26:341-55.
  8. Ong SB, Samangouei P, Kalkhoran SB, Hausenloy DJ. The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury. J Mol Cell Cardiol 2015;78:23-34.
  9. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB. The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation 1977;56:786-94.
  10. Cohen MV, Downey JM. Combined cardioprotectant and antithrombotic actions of platelet P2Y12 receptor antagonists in acute coronary syndrome: just what the doctor ordered. J Cardiovasc Pharmacol Ther 2014;19:179-90.
  11. Cohen MV, Downey JM. The impact of irreproducibility and competing protection from P2Y12 antagonists on the discovery of cardioprotective interventions. Basic Res Cardiol 2017;112:64.
  12. Mirabet M, Garcia-Dorado D, Inserte J, et al. Platelets activated by transient coronary occlusion exacerbate ischemia-reperfusion injury in rat hearts. Am J Physiol Heart Circ Physiol 2002;283:H1134-41.
  13. Ault KA, Cannon CP, Mitchell J, et al. Platelet activation in patients after an acute coronary syndrome: results from the TIMI-12 trial. Thrombolysis in Myocardial Infarction. J Am Coll Cardiol 1999;33:634-9.
  14. Langford EJ, Wainwright RJ, Martin JF. Platelet activation in acute myocardial infarction and unstable angina is inhibited by nitric oxide donors. Arterioscler Thromb Vasc Biol 1996;16:51-5.
  15. Russo I, Femmino S, Barale C, et al. Cardioprotective properties of human platelets are lost in uncontrolled diabetes mellitus: a study in isolated rat hearts. Front Physiol 2018;9:875.
  16. Heusch G. Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 2015;116:674-99.
  17. Heusch G. Myocardial ischaemia-reperfusion injury and cardioprotection in perspective. Nat Rev Cardiol 2020;17:773-89.
  18. Yellon DM, Downey JM. Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 2003;83:1113-51.
  19. Yang XM, Liu Y, Cui L, et al. Platelet P2Y12 blockers confer direct postconditioning-like protection in reperfused rabbit hearts. J Cardiovasc Pharmacol Ther 2013;18:251-62.
  20. Birnbaum Y, Lin Y, Ye Y, et al. Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin. Am J Physiol Heart Circ Physiol 2007;292:H2891-7.
  21. Gross ER, Hsu AK, Gross GJ. Acute aspirin treatment abolishes, whereas acute ibuprofen treatment enhances morphine-induced cardioprotection: role of 12-lipoxygenase. J Pharmacol Exp Ther 2004;310:185-91.
  22. Ye Y, Birnbaum GD, Perez-Polo JR, Nanhwan MK, Nylander S, Birnbaum Y. Ticagrelor protects the heart against reperfusion injury and improves remodeling after myocardial infarction. Arterioscler Thromb Vasc Biol 2015;35:1805-14.
  23. Cattaneo M. P2Y12 receptors: structure and function. J Thromb Haemost 2015;13 Suppl 1:S10-6.
  24. Djerada Z, Feliu C, Richard V, Millart H. Current knowledge on the role of P2Y receptors in cardioprotection against ischemia-reperfusion. Pharmacol Res 2017;118:5-18.
  25. Cattaneo M. New P2Y12 inhibitors. Circulation 2010;121:171-9.
  26. Barrabes JA, Inserte J, Mirabet M, et al. Antagonism of P2Y12 or GPIIb/IIIa receptors reduces platelet-mediated myocardial injury after ischaemia and reperfusion in isolated rat hearts. Thromb Haemost 2010;104:128-35.
  27. Yang XM, Cui L, Alhammouri A, Downey JM, Cohen MV. Triple therapy greatly increases myocardial salvage during ischemia/reperfusion in the in situ rat heart. Cardiovasc Drugs Ther 2013;27:403-12.
  28. Audia JP, Yang XM, Crockett ES, et al. Caspase-1 inhibition by VX-765 administered at reperfusion in P2Y12 receptor antagonist-treated rats provides long-term reduction in myocardial infarct size and preservation of ventricular function. Basic Res Cardiol 2018;113:32.
  29. Liu X, Gu Y, Liu Y, Zhang M, Wang Y, Hu L. Ticagrelor attenuates myocardial ischaemia-reperfusion injury possibly through downregulating galectin-3 expression in the infarct area of rats. Br J Clin Pharmacol 2018;84:1180-6.
  30. Armstrong D, Summers C, Ewart L, Nylander S, Sidaway JE, van Giezen JJ. Characterization of the adenosine pharmacology of ticagrelor reveals therapeutically relevant inhibition of equilibrative nucleoside transporter 1. J Cardiovasc Pharmacol Ther 2014;19:209-19.
  31. Yang XM, Gadde S, Audia JP, Alvarez DF, Downey JM, Cohen MV. Ticagrelor does not protect isolated rat hearts, thus clouding its proposed cardioprotective role through ENT 1 in heart tissue. J Cardiovasc Pharmacol Ther 2019;24:371-6.
  32. Yang XM, Liu Y, Cui L, et al. Two classes of anti-platelet drugs reduce anatomical infarct size in monkey hearts. Cardiovasc Drugs Ther 2013;27:109-15.
  33. Liu X, Wang Y, Zhang M, Liu Y, Hu L, Gu Y. Ticagrelor reduces ischemia-reperfusion injury through the NF-κB-dependent pathway in rats. J Cardiovasc Pharmacol 2019;74:13-9.
  34. Maslov LN, Popov SV, Mukhomedzyanov AV, et al. Reperfusion cardiac injury: receptors and the signaling mechanisms. Curr Cardiol Rev. 2022 [Epub ahead of print].
  35. Vilahur G, Gutierrez M, Casani L, et al. P2Y12 antagonists and cardiac repair post-myocardial infarction: global and regional heart function analysis and molecular assessments in pigs. Cardiovasc Res 2018;114:1860-70.
  36. Birnbaum Y, Tran D, Chen H, Nylander S, Sampaio LC, Ye Y. Ticagrelor improves remodeling, reduces apoptosis, inflammation and fibrosis and increases the number of progenitor stem cells after myocardial infarction in a rat model of ischemia reperfusion. Cell Physiol Biochem 2019;53:961-81.
  37. Xie ZJ, Xin SL, Chang C, et al. Combined glycoprotein IIb/IIIa inhibitor therapy with ticagrelor for patients with acute coronary syndrome. PLoS One 2021;16:e0246166.
  38. Yang XM, Downey JM, Cohen MV, Housley NA, Alvarez DF, Audia JP. The highly selective caspase-1 inhibitor VX-765 provides additive protection against myocardial infarction in rat hearts when combined with a platelet inhibitor. J Cardiovasc Pharmacol Ther 2017;22:574-8.
  39. Hjortbak MV, Olesen KKW, Seefeldt JM, et al. Translation of experimental cardioprotective capability of P2Y12 inhibitors into clinical outcome in patients with ST-elevation myocardial infarction. Basic Res Cardiol 2021;116:36.
  40. Penna C, Aragno M, Cento AS, et al. Ticagrelor conditioning effects are not additive to cardioprotection induced by direct NLRP3 inflammasome inhibition: role of RISK, NLRP3, and redox cascades. Oxid Med Cell Longev 2020;2020:9219825.
  41. Cohen MV, Yang XM, White J, Yellon DM, Bell RM, Downey JM. Cangrelor-mediated cardioprotection requires platelets and sphingosine phosphorylation. Cardiovasc Drugs Ther 2016;30:229-32.
  42. Ahmed N, Linardi D, Muhammad N, et al. Sphingosine 1-phosphate receptor modulator fingolimod (FTY720) attenuates myocardial fibrosis in post-heterotopic heart transplantation. Front Pharmacol 2017;8:645.
  43. Chen R, Cai X, Liu J, Bai B, Li X. Sphingosine 1-phosphate promotes mesenchymal stem cell-mediated cardioprotection against myocardial infarction via ERK1/2-MMP-9 and Akt signaling axis. Life Sci 2018;215:31-42.
  44. Knapp M. Cardioprotective role of sphingosine-1-phosphate. J Physiol Pharmacol 2011;62:601-7.
  45. Jin ZQ, Zhou HZ, Zhu P, et al. Cardioprotection mediated by sphingosine-1-phosphate and ganglioside GM-1 in wild-type and PKC epsilon knockout mouse hearts. Am J Physiol Heart Circ Physiol 2002;282:H1970-7.
  46. Means CK, Xiao CY, Li Z, et al. Sphingosine 1-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2007;292:H2944-51.
  47. Vessey DA, Li L, Kelley M, Karliner JS. Combined sphingosine, S1P and ischemic postconditioning rescue the heart after protracted ischemia. Biochem Biophys Res Commun 2008;375:425-9.
  48. Hofmann U, Burkard N, Vogt C, et al. Protective effects of sphingosine-1-phosphate receptor agonist treatment after myocardial ischaemia-reperfusion. Cardiovasc Res 2009;83:285-93.
  49. Marino A, Sakamoto T, Robador PA, Tomita K, Levi R. S1P receptor 1-mediated anti-renin-angiotensin system cardioprotection: pivotal role of mast cell aldehyde dehydrogenase type 2. J Pharmacol Exp Ther 2017;362:230-42.
  50. Kuai F, Wang L, Su J, Wang Y, Han Y, Zhou S. Exploring the protective role and the mechanism of sphingosine 1 phosphate in endotoxic cardiomyocytes. Shock 2019;52:468-76.
  51. Spampinato SF, Sortino MA, Salomone S. Sphingosine-1-phosphate and sphingosine-1-phosphate receptors in the cardiovascular system: pharmacology and clinical implications. Adv Pharmacol 2022;94:95-139.
  52. Kelly-Laubscher RF, King JC, Hacking D, et al. Cardiac preconditioning with sphingosine-1-phosphate requires activation of signal transducer and activator of transcription-3. Cardiovasc J S Afr 2014;25:118-23.
  53. Fang R, Zhang LL, Zhang LZ, Li W, Li M, Wen K. Sphingosine 1-phosphate postconditioning protects against myocardial ischemia/reperfusion injury in rats via mitochondrial signaling and Akt-Gsk3β phosphorylation. Arch Med Res 2017;48:147-55.
  54. Chawla S, Rahar B, Saxena S. S1P prophylaxis mitigates acute hypobaric hypoxia-induced molecular, biochemical, and metabolic disturbances: a preclinical report. IUBMB Life 2016;68:365-75.
  55. Rutherford C, Childs S, Ohotski J, et al. Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of Bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1. Cell Death Dis 2013;4:e927.
  56. Somers SJ, Frias M, Lacerda L, Opie LH, Lecour S. Interplay between SAFE and RISK pathways in sphingosine-1-phosphate-induced cardioprotection. Cardiovasc Drugs Ther 2012;26:227-37.
  57. Kuang Y, Li X, Liu X, et al. Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction. Cardiovasc Res 2021;117:585-99.
  58. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502.
  59. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366:1607-21.
  60. Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005;294:1224-32.
  61. Lewis BS, Mehta SR, Fox KA, et al. Benefit of clopidogrel according to timing of percutaneous coronary intervention in patients with acute coronary syndromes: further results from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Am Heart J 2005;150:1177-84.
  62. Dangas G, Mehran R, Guagliumi G, et al. Role of clopidogrel loading dose in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty: results from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. J Am Coll Cardiol 2009;54:1438-46.
  63. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-57.
  64. Witkowski A, Maciejewski P, Wasek W, et al. Influence of different antiplatelet treatment regimens for primary percutaneous coronary intervention on all-cause mortality. Eur Heart J 2009;30:1736-43.
  65. Song YB, Hahn JY, Gwon HC, et al. A high loading dose of clopidogrel reduces myocardial infarct size in patients undergoing primary percutaneous coronary intervention: a magnetic resonance imaging study. Am Heart J 2012;163:500-7.
  66. Leonardi S, Stebbins A, Lopes RD, et al. Quantification of the effect of clopidogrel on enzymatic infarct size related to a percutaneous coronary intervention in patients with acute coronary syndromes: insights from the CHAMPION percutaneous coronary intervention trial. Coron Artery Dis 2013;24:321-7.
  67. Serebruany VL, Cherepanov V, Tomek A, Kim MH. Among antithrombotic agents, prasugrel, but not ticagrelor, is associated with reduced 30 day mortality in patients with ST-elevated myocardial infarction. Int J Cardiol 2015;195:104-10.
  68. Kang HJ, Clare RM, Gao R, et al. Ticagrelor versus clopidogrel in Asian patients with acute coronary syndrome: a retrospective analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial. Am Heart J 2015;169:899-905.e1.
  69. Goto S, Huang CH, Park SJ, Emanuelsson H, Kimura T. Ticagrelor vs. clopidogrel in Japanese, Korean and Taiwanese patients with acute coronary syndrome -- randomized, double-blind, phase III PHILO study. Circ J 2015;79:2452-60.
  70. Khan JN, Greenwood JP, Nazir SA, et al. Infarct size following treatment with second- versus third-generation P2Y12 antagonists in patients with multivessel coronary disease at ST-segment elevation myocardial infarction in the CvLPRIT study. J Am Heart Assoc 2016;5:e003403.
  71. Yun KH, Rhee SJ, Ko JS. Comparison of the infarct size between the loading of ticagrelor and clopidogrel in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Korean Circ J 2017;47:705-13.
  72. Huber K, Ducrocq G, Hamm CW, et al. Early clinical outcomes as a function of use of newer oral P2Y12 inhibitors versus clopidogrel in the EUROMAX trial. Open Heart 2017;4:e000677.
  73. Kang J, Han JK, Ahn Y, et al. Third-generation P2Y12 inhibitors in East Asian acute myocardial infarction patients: a nationwide prospective multicentre study. Thromb Haemost 2018;118:591-600.
  74. Gao R, Wu Y, Liu H, et al. Safety and incidence of cardiovascular events in chinese patients with acute coronary syndrome treated with ticagrelor: the 12-month, phase IV, multicenter, single-arm DAYU study. Cardiovasc Drugs Ther 2018;32:47-56.
  75. Ubaid S, Ford TJ, Berry C, et al. Cangrelor versus ticagrelor in patients treated with primary percutaneous coronary intervention: impact on platelet activity, myocardial microvascular function and infarct size: a randomized controlled trial. Thromb Haemost 2019;119:1171-81.
  76. Dworeck C, Redfors B, Angeras O, et al. Association of pretreatment with P2Y12 receptor antagonists preceding percutaneous coronary intervention in non-ST-segment elevation acute coronary syndromes with outcomes. JAMA Netw Open 2020;3:e2018735.
  77. Moura Guedes JP, Marques N, Azevedo P, et al. P2Y12 inhibitor loading dose before catheterization in ST-segment elevation myocardial infarction: is this the best strategy? Rev Port Cardiol (Engl Ed) 2020;39:553-61.
  78. Al Raisi S, Protty M, Raposeiras-Roubin S, et al. Ticagrelor versus prasugrel in acute coronary syndrome: sex-specific analysis from the RENAMI registry. Minerva Cardiol Angiol 2021;69:408-16.
  79. Park Y, Koh JS, Lee JH, et al. Effect of ticagrelor on left ventricular remodeling in patients with ST-segment elevation myocardial infarction (HEALING-AMI). JACC Cardiovasc Interv 2020;13:2220-34.