Influence of platelet count on the expression of platelet collagen receptor glycoprotein VI (GPVI) in patients with acute coronary syndrome

Summary

Platelets play a key role in the development of an acute coronary syndrome (ACS) and contribute to cardiovascular events. Platelet collagen receptor glycoprotein VI (GPVI) contributes significantly to platelet adhesion and thrombus formation in ACS. We consecutively investigated both the platelet count and the platelet surface expression of GPVI in 843 patients with a symptomatic coronary artery disease verified by coronary angiography. Four hundred fourteen patients presented with stable angina pectoris and 429 patients with ACS. Platelet surface expression of GPVI and CD62P was determined by flow cytometry and platelet count with a coulter counter, plasmatic soluble GPVI was measured by ELISA. Platelet GPVI expression in patients with ACS was compared to platelet count. Patients with ACS showed significantly elevated GPVI expression levels in the first and second quartiles of platelet count compared to patients with higher platelet count [mean fluorescence intensity (MFI) ± standard deviation): 1^st vs. 4^th: 20.44 ± 6.1 vs. 18.62 ± 3.7; p=0.012; 2^ndvs.3^rd:21.2±8.5vs.18.76±3.7;P=0.03; 2^ndvs.4^th: 21.2±8.5vs.18.62±3.7;P=0.004], which was paralleled in trend for the CD62P expression [MFI: 1^st vs. 4^th: 11.2 ± 6.8 vs. 12.3 ± 9; p=0.057; 2^nd vs. 3^rd: 16.3 ± 16 vs.12.7 ± 5.3; p=0.138; 2^nd vs. 4^th: 16.3 ± 16 vs.11 ± 4.4; p=0.043]. In a subgroup of 48 patients with ACS, determination of soluble GPVI showed similar results [plasma GPVI (ng/ml): 1^stvs.4^th: 1.6 ± 0.6 vs. 1.2 ± 0.4; p=0.046; 1^st vs. 3^rd: 1.6 ± 0.6 vs. 1.1 ± 0.5; p=0.038; 2^nd vs. 3^rd: 1.9 ± 0.8 vs. 1.1 ± 0.5; p=0.04; 2^nd vs. 4^th: 1.9 ± 0.8 vs. 1.2 ± 0.4; p=0.056]. Thus, a lower platelet count comes along with a higher GPVI surface expression and plasma concentration in patients with ACS, which potentially reflects increased activation and enhanced recruitment of platelets to the site of vascular injury.

Keywords

Platelet count - glycoprotein VI - acute coronary syndrome

• References

• 1 Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357: 2482-2494.
• 2 Anderson JL, Adams CD, Antman EM. et al. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/ Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation 2007; 116: e148-304.
• 3 Hamm CW, Goldmann BU, Heeschen C. et al. Emergency room triage with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997; 337: 1648-1653.
• 4 Liuzzo G, Biasucci LM, Gallimore JR. et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994; 331: 417-424.
• 5 Heeschen C, Dimmeler S, Hamm CW. et al. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med 2003; 348: 1104-1111.
• 6 de Lemos JA, Morrow DA, Bentley JH. et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001; 345: 1014-1021.
• 7 Viallard JF, Solanilla A, Gauthier B. et al. Increased soluble and platelet-associated CD40 ligand in essential thrombocythemia and reactive thrombocytosis. Blood 2002; 99: 2612-2614.
• 8 Järemo P, Hansson G, Nilsson O. Elevated inflammatory parameters are associated with lower platelet density in acute myocardial infarctions with ST-elevation. Thromb Res 2000; 100: 471-478.
• 9 Zakai NA, Katz R, Jenny NS. et al. Inflammation and hemostasis biomarkers and cardiovascular risk in the elderly: the Cardiovascular Health Study. J Thromb Haemost 2007; 05: 1128-1135.
• 10 Tschoepe D, Schultheiss HP, Kolarov P. et al. Platelet membrane activation markers are predictive for increased risk of acute ischemic events after PTCA. Circulation 1993; 88: 37-42.
• 11 Gawaz M, Neumann FJ, Ott I. et al. Platelet function in acute myocardial infarction treated with direct angioplasty. Circulation 1996; 93: 229-237.
• 12 Neumann FJ, Kósa I, Dickfeld T. et al. Recovery of myocardial perfusion in acute myocardial infarction after successful balloon angioplasty and stent placement in the infarct-related coronary artery. J Am Coll Cardiol 1997; 30: 1270-1276.
• 13 Samaha FF, Hibbard C, Sacks J. et al. Density of platelet collagen receptors glycoprotein VI and alpha2beta1 and prior myocardial infarction in human subjects, a pilot study. Med Sci Monit 2005; 11: CR224-229.
• 14 Fateh-Moghadam S, Htun P, Tomandl B. et al. Hyperresponsiveness of platelets in ischemic stroke. Thromb Haemost 2007; 97: 974-978.
• 15 McEver RP. Role of selectins in leukocyte adhesion to platelets and endothelium. Ann NY Acad Sci 1994; 714: 185-189.
• 16 Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor?. Blood 2003; 102: 449-461.
• 17 Jung SM, Takemura Y, Imamura Y. et al. Collagen-type specificity of glycoprotein VI as a determinant of platelet adhesion. Platelets 2008; 19: 32-42.
• 18 Bigalke B, Lindemann S, Ehlers R. et al. Expression of platelet collagen receptor VI is associated with acute coronary syndrome. Eur Heart J 2006; 27: 2165-2169.
• 19 Bigalke B, Geisler T, Stellos K. et al. Platelet collagen receptor glycoprotein VI as a possible novel indicator for the acute coronary syndrome. Am Heart J 2008; 156: 193-200.
• 20 Laske C, Leyhe T, Stransky E. et al. Association of platelet-derived soluble glycoprotein VI in plasma with Alzheimer’s disease. J Psychiatr Res 2008; 42: 746-751.
• 21 Gawaz M, Neumann FJ, Schomig A. Evaluation of platelet membrane glycoproteins in coronary artery disease: consequences for diagnosis and therapy. Circulation 1999; 99: E1-E11.
• 22 Fateh-Moghadam S, Bocksch W, Ruf A. et al. Changes in surface expression of platelet membrane glycoproteins and progression of heart transplant vasculopathy. Circulation 2000; 102: 890-897.
• 23 Cabeza N, Li Z, Schulz C. et al. Surface expression of collagen receptor Fc receptor-gamma/glycoprotein VI is enhanced on platelets in type 2 diabetes and mediates release of CD40 ligand and activation of endothelial cells. Diabetes 2004; 53: 2117-2121.
• 24 Massberg S, Konrad I, Bültmann A. et al. Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo. FASEB J 2004; 18: 397-399.
• 25 Bergmeier W, Rabie T, Strehl A. et al. GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding. Thromb Haemost 2004; 91: 951-958.
• 26 Gardiner EE, Arthur JF, Kahn ML. et al. Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase. Blood 2004; 104: 3611-3617.
• 27 Rabie T, Varga-Szabo D, Bender M. et al. Diverging signaling events control the pathway of GPVI down-regulation in vivo. Blood 2007; 110: 529-535.
• 28 Stephens G, Yan Y, Jandrot-Perrus M. et al. Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen. Blood 2005; 105: 186-191.
• 29 Bültmann A, Herdeg C, Li Z. et al. Local delivery of soluble platelet collagen receptor.
• 30 glycoprotein VI inhibits thrombus formation in vivo. Thromb Haemost 2006; 95: 763-766.
• 31 Mueller C, Neumann FJ, Hochholzer W. et al. The impact of platelet count on mortality in unstable angina/non-ST-segment elevation myocardial infarction. Am Heart J 2006; 151: 1214.e1-7.
• 32 Aleil B, Meyer N, Wolff V. et al. Plasma glycoprotein V levels in the general population: normal distribution, associated parameters and implications for clinical studies. Thromb Haemost 2006; 96: 505-511.
• 33 Aleil B, Kessler L, Meyer N. et al. Plasma levels of soluble platelet glycoprotein V are linked to fasting blood glucose in patients with type 2 diabetes. Thromb Haemost 2008; 100: 713-715.
• 34 Langer H, May AE, Bültmann A. et al. ADAM 15 is an adhesion receptor for platelet GPIIb-IIIa and induces platelet activation. Thromb Haemost 2005; 94: 555-561.
• 35 Sjauw KD, van der Horst IC, Nijsten MW. et al. Value of routine admission laboratory tests to predict thirty-day mortality in patients with acute myocardial infarction. Am J Cardiol 2006; 97: 1435-1440.
• 36 Wong CK, French JK, Gao W. et al. Relation of initial platelet counts to Thrombolysis In Myocardial Infarction-3 flow rates at 90 minutes after commencing fibrinolytic therapy in patients with acute myocardial infarction. Am J Cardiol 2002; 90: 54-57.
• 37 Burr ML, Holliday RM, Fehily AM. et al. Haemato-logical prognostic indices after myocardial infarction: evidence from the diet and reinfarction trial (DART). Eur Heart J 1992; 13: 166-170.
• 38 Johansen O, Brekke M, Seljeflot I. et al. Blood platelet count and reactivity are associated with restenosis 6 months after coronary angioplasty. Scand Cardiovasc J 2004; 38: 211-215.
• 39 Iijima R, Ndrepepa G, Mehilli J. et al. Relationship between platelet count and 30-day clinical outcomes after percutaneous coronary interventions. Pooled analysis of four ISAR trials. Thromb Haemost 2007; 98: 852-857.