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IIIa antagonists and inflammation
International Journal of Cardiology 94 (2004) 121 – 122 www.elsevier.com/locate/ijcard
Letter to the Editor
Specific glycoprotein IIb/IIIa antagonists and inflammation E. Ercan * Department of Cardiology, Central Hospital Institute, 1644 sk. NO: 2/2 Bayrakli, Izmir 35000, Turkey
Acute coronary syndromes and coronary balloon angioplasty (PTCA) are associated with increased coagulatory and inflammatory activity [1– 6]. The levels of cytokines and chemokines, which are released to inflammatory response, can be used to evaluate the severity of inflammation. C-reactive protein, soluble adhesion molecules, and interleukins are some of the important markers of inflammation [7]. The main effect of glycoprotein IIb/IIIa inhibitors is their strong anti-platelet effect, which has been clinically proven in large-scale randomised trials [8 –12]. Recent studies have indicated that glycoprotein IIb/IIIa antagonist treatment can decrease inflammatory activity [13]. But it is not clear that this beneficial effect is restricted to nonspecific glycoprotein IIb/IIIa blockers. There are two reports with specific glycoprotein IIb/IIIa antagonists that describe anti-inflammatory effect in unstable angina (Tirofiban) and after PTCA (Eptifibatide) [14,15]. Different effect mechanisms may explain the anti-inflammatory effect of specific glycoprotein Ib/IIIa antagonists.
1. Platelet activation and inflammation Platelet activation can increase inflammation through multiple mechanisms. Inflammatory proteins such as pselectin (CD62p), CD40p, PAF, MCP-1, IL-1, thrombospondin and fibronectin are rapidly expressed from activated platelets. Products of platelet activation may aid neutrophil accumulation at inflammatory sites. Activated leukocytes and platelets potentiate each others effects [16 – 20]. Specific glycoprotein IIb/IIIa antagonists strongly suppress the activation of platelets by specific blockade of the fibrinogen binding receptor [21 –23]. The decreased platelet activation can suppress the chemokine and adhesion molecule expression. The relationship between inflammation and coagulation system may be mediated through the surface protein and cytokine production.
* Tel.: +90-533-521-6481; fax: +90-232-345-3456. E-mail address: [email protected] (E. Ercan). 0167-5273/$ - see front matter D 2003 Published by Elsevier Ireland Ltd. doi:10.1016/j.ijcard.2003.03.008
2. Conclusion Specific glycoprotein IIb/IIIa inhibitors may show antiinflammatory effect via decreased platelet activation. Crossreactivity is not the unique mechanism that explains antiinflammatory effect of glycoprotein IIb/IIIa antagonists.
References [1] Serrano Jr CV, Ramires JA, Venturinelli M, Arie S, D’Amico E, Zweier JL, et al. Coronary angioplasty results in leukocyte and platelet activation with adhesion molecule expression. Evidence of inflammatory responses in coronary angioplasty. J Am Coll Cardiol 1997 (May);29(6):1276 – 83. [2] Freedman JE, Loscalzo J. Platelet-monocyte aggregates: bridging thrombosis and inflammation. Circulation 2002 (May);105:2130 – 2. [3] Sarma J, Laan CA, Alam S, Jha A, Fox KA, Dransfield I. Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 2002 (May);105:2166 – 71. [4] Buja LM, Willerson JT. Role of inflammation in coronary plaque disruption. Circulation 1994;89:503 – 5. [5] Fuster V, Chesebro JH. Mechanism of unstable angina. N Engl J Med 1986;315:1023 – 4. [6] Hezard N, Metz D, Garnotel R, Droulle C, Potron G, Nguyen P. Platelet – leukocyte interactions in coronary heart disease: pathophysiology, clinical relevance, pharmacological modulation. J Mal Vasc 2000 (Dec);25(5):343 – 8. [7] Lente FV. Markers of inflammation as predictors in cardiovascular medicine. Clin Chim Acta 2000;293:31 – 52. [8] The CAPTURE Investigators. Randomized Placebo controlled trial of abciximab before and during coronary intervention in refractor unstable angina. Lancet 1997;349:1623 – 9. [9] The PURSUIT Trial investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med 1998;339(7):436 – 43. [10] The PRISM Investigators. A comparison of Aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998; 338:1498 – 505. [11] The PRISM-PLUS Investigators. I˙nhibition of platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non Q wave myocardial infarction. N Engl J Med 1998;338:1488 – 97. [12] The PARAGON investigators. International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin or both in unstable angina Platelet IIb/IIIa Antagonism for the reduction of Accute coronary syndrome events in a Global Organization Network. Circulation 1998;97(24):2386 – 95.
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E. Ercan / International Journal of Cardiology 94 (2004) 121–122
[13] Lincoff AM, Kereiakes DJ, Mascelli MA, et al. Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization. Circulation 2001;104:163 – 7. [14] Ercan E., Bozdemir H., Ceyhan C., Tekten T., Onbasi A., Altuglu I., et al. Glycoprotein IIb/IIIa antagonists and inflammation: a new effect mechanism in patients with unstable angina pectoris. Berlin: European Society of Cardiology Congress; 2002. [15] Merino A, Artaiz M, Alinz I, Segura I, Inigo V, Vidal B, et al. Eptifibatide blocks the increase in C-reactive protein levels induced by coronary angioplasty. Berlin: European Society of Cardiology Congress; 2002. [16] Zimmerman GA, Mclntyre TM, Prescott SM, Stafforini DM. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med 2002 (May);30:294 – 301. [17] Gawaz M, Neumann F-J, Dickfeld T, Reininger A, Adelsberger H, Gebhardt A, et al. Vitronectin receptor mediates platelet adhesion to the luminal aspects of endothelial cells. Circulation 1997;96:1809 – 18. [18] Mazzone A, De Servi S, Ricevuti G, Mazzucchelli I, Fossati G, Pasotti D, et al. Increased expression of neutrophil and monocyte
[19]
[20] [21]
[22] [23]
adhesion molecules in unstable coronary artery disease. Circulation 1993;88:358 – 63. Weyrich AS, Elstad MR, McEver RP, McIntyre TM, Moore KL, Morrissey JH, Prescott SM, Zimmerman GA. Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 1996;97(6):1525 – 34. Freedman JE, Loscalzo J. Platelet-monocyte aggregates: bridging thrombosis and inflammation. Circulation 2002 (May);105:2130 – 2. Bertram U, Moser M, Peter K, Kuecherer HF, Bekeredjian R, Straub A, Nordt TK, Bode C, Ruef J. Effects of different thrombolytic treatment regimen with abciximab and tirofiban on platelet aggregation and platelet-leukocyte interactions: a subgroup analysis from the GUSTO V and FASTER trials. J Thromb Thrombolysis 2002;14(3):197 – 203. Madan M, Berkowitz SD, Tcheng JE. Glycoprotein IIb/IIIa integrin blockade. Circulation 1998;98:2629 – 35. Mak KH, Tan AT, Chan C, et al. The clinical impact of platelet glycoprotein IIb/IIIa receptor blockade in cardiovascular medicine. Jpn Circ 1998;J 62:233 – 43.
Letter to the Editor
Specific glycoprotein IIb/IIIa antagonists and inflammation E. Ercan * Department of Cardiology, Central Hospital Institute, 1644 sk. NO: 2/2 Bayrakli, Izmir 35000, Turkey
Acute coronary syndromes and coronary balloon angioplasty (PTCA) are associated with increased coagulatory and inflammatory activity [1– 6]. The levels of cytokines and chemokines, which are released to inflammatory response, can be used to evaluate the severity of inflammation. C-reactive protein, soluble adhesion molecules, and interleukins are some of the important markers of inflammation [7]. The main effect of glycoprotein IIb/IIIa inhibitors is their strong anti-platelet effect, which has been clinically proven in large-scale randomised trials [8 –12]. Recent studies have indicated that glycoprotein IIb/IIIa antagonist treatment can decrease inflammatory activity [13]. But it is not clear that this beneficial effect is restricted to nonspecific glycoprotein IIb/IIIa blockers. There are two reports with specific glycoprotein IIb/IIIa antagonists that describe anti-inflammatory effect in unstable angina (Tirofiban) and after PTCA (Eptifibatide) [14,15]. Different effect mechanisms may explain the anti-inflammatory effect of specific glycoprotein Ib/IIIa antagonists.
1. Platelet activation and inflammation Platelet activation can increase inflammation through multiple mechanisms. Inflammatory proteins such as pselectin (CD62p), CD40p, PAF, MCP-1, IL-1, thrombospondin and fibronectin are rapidly expressed from activated platelets. Products of platelet activation may aid neutrophil accumulation at inflammatory sites. Activated leukocytes and platelets potentiate each others effects [16 – 20]. Specific glycoprotein IIb/IIIa antagonists strongly suppress the activation of platelets by specific blockade of the fibrinogen binding receptor [21 –23]. The decreased platelet activation can suppress the chemokine and adhesion molecule expression. The relationship between inflammation and coagulation system may be mediated through the surface protein and cytokine production.
* Tel.: +90-533-521-6481; fax: +90-232-345-3456. E-mail address: [email protected] (E. Ercan). 0167-5273/$ - see front matter D 2003 Published by Elsevier Ireland Ltd. doi:10.1016/j.ijcard.2003.03.008
2. Conclusion Specific glycoprotein IIb/IIIa inhibitors may show antiinflammatory effect via decreased platelet activation. Crossreactivity is not the unique mechanism that explains antiinflammatory effect of glycoprotein IIb/IIIa antagonists.
References [1] Serrano Jr CV, Ramires JA, Venturinelli M, Arie S, D’Amico E, Zweier JL, et al. Coronary angioplasty results in leukocyte and platelet activation with adhesion molecule expression. Evidence of inflammatory responses in coronary angioplasty. J Am Coll Cardiol 1997 (May);29(6):1276 – 83. [2] Freedman JE, Loscalzo J. Platelet-monocyte aggregates: bridging thrombosis and inflammation. Circulation 2002 (May);105:2130 – 2. [3] Sarma J, Laan CA, Alam S, Jha A, Fox KA, Dransfield I. Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 2002 (May);105:2166 – 71. [4] Buja LM, Willerson JT. Role of inflammation in coronary plaque disruption. Circulation 1994;89:503 – 5. [5] Fuster V, Chesebro JH. Mechanism of unstable angina. N Engl J Med 1986;315:1023 – 4. [6] Hezard N, Metz D, Garnotel R, Droulle C, Potron G, Nguyen P. Platelet – leukocyte interactions in coronary heart disease: pathophysiology, clinical relevance, pharmacological modulation. J Mal Vasc 2000 (Dec);25(5):343 – 8. [7] Lente FV. Markers of inflammation as predictors in cardiovascular medicine. Clin Chim Acta 2000;293:31 – 52. [8] The CAPTURE Investigators. Randomized Placebo controlled trial of abciximab before and during coronary intervention in refractor unstable angina. Lancet 1997;349:1623 – 9. [9] The PURSUIT Trial investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med 1998;339(7):436 – 43. [10] The PRISM Investigators. A comparison of Aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998; 338:1498 – 505. [11] The PRISM-PLUS Investigators. I˙nhibition of platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non Q wave myocardial infarction. N Engl J Med 1998;338:1488 – 97. [12] The PARAGON investigators. International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin or both in unstable angina Platelet IIb/IIIa Antagonism for the reduction of Accute coronary syndrome events in a Global Organization Network. Circulation 1998;97(24):2386 – 95.
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E. Ercan / International Journal of Cardiology 94 (2004) 121–122
[13] Lincoff AM, Kereiakes DJ, Mascelli MA, et al. Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization. Circulation 2001;104:163 – 7. [14] Ercan E., Bozdemir H., Ceyhan C., Tekten T., Onbasi A., Altuglu I., et al. Glycoprotein IIb/IIIa antagonists and inflammation: a new effect mechanism in patients with unstable angina pectoris. Berlin: European Society of Cardiology Congress; 2002. [15] Merino A, Artaiz M, Alinz I, Segura I, Inigo V, Vidal B, et al. Eptifibatide blocks the increase in C-reactive protein levels induced by coronary angioplasty. Berlin: European Society of Cardiology Congress; 2002. [16] Zimmerman GA, Mclntyre TM, Prescott SM, Stafforini DM. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med 2002 (May);30:294 – 301. [17] Gawaz M, Neumann F-J, Dickfeld T, Reininger A, Adelsberger H, Gebhardt A, et al. Vitronectin receptor mediates platelet adhesion to the luminal aspects of endothelial cells. Circulation 1997;96:1809 – 18. [18] Mazzone A, De Servi S, Ricevuti G, Mazzucchelli I, Fossati G, Pasotti D, et al. Increased expression of neutrophil and monocyte
[19]
[20] [21]
[22] [23]
adhesion molecules in unstable coronary artery disease. Circulation 1993;88:358 – 63. Weyrich AS, Elstad MR, McEver RP, McIntyre TM, Moore KL, Morrissey JH, Prescott SM, Zimmerman GA. Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 1996;97(6):1525 – 34. Freedman JE, Loscalzo J. Platelet-monocyte aggregates: bridging thrombosis and inflammation. Circulation 2002 (May);105:2130 – 2. Bertram U, Moser M, Peter K, Kuecherer HF, Bekeredjian R, Straub A, Nordt TK, Bode C, Ruef J. Effects of different thrombolytic treatment regimen with abciximab and tirofiban on platelet aggregation and platelet-leukocyte interactions: a subgroup analysis from the GUSTO V and FASTER trials. J Thromb Thrombolysis 2002;14(3):197 – 203. Madan M, Berkowitz SD, Tcheng JE. Glycoprotein IIb/IIIa integrin blockade. Circulation 1998;98:2629 – 35. Mak KH, Tan AT, Chan C, et al. The clinical impact of platelet glycoprotein IIb/IIIa receptor blockade in cardiovascular medicine. Jpn Circ 1998;J 62:233 – 43.