Platelet Glycoprotein VI: A Novel Marker for Acute Coronary Syndrome

ABSTRACT

The platelet collagen receptor glycoprotein (GP) VI is critical for the formation of arterial thrombosis. GPVI platelet surface expression was examined in patients with stable angina and in patients with acute coronary syndrome (ACS). Surface expression of platelet activation markers such as P-selectin, GPIbα, and platelet GPVI was determined by flow cytometry. Patients with ACS showed a significantly enhanced GPVI expression compared with patients with stable angina and healthy controls. The expression of GPVI correlated well with CD62P. Elevated platelet GPVI expression was associated with ACS independent of markers of myocardial necrosis such as troponin and creatine kinase. In ACS, platelet surface GPVI expression was already elevated several hours before troponin and creatine kinase indicated myocardial injury. We conclude that the determination of the platelet-specific thrombotic marker GPVI may help to identify patients at risk before myocardial ischemia is evident.

KEYWORDS

Platelets - glycoprotein (GP) VI - collagen - acute coronary syndrome

REFERENCES

• 1 Ruggeri Z M. Platelets in atherothrombosis.  Nat Med. 2002;  8(11) 1227-1234
• 2 Nieswandt B, Watson S P. Platelet-collagen interaction: is GPVI the central receptor?.  Blood. 2003;  102(2) 449-461
• 3 Kahn M L. Platelet-collagen responses: molecular basis and therapeutic promise.  Semin Thromb Hemost. 2004;  30(4) 419-425
• 4 Moroi M, Jung S M. Platelet glycoprotein VI: its structure and function.  Thromb Res. 2004;  114(4) 221-233
• 5 Boylan B, Chen H, Rathore V et al.. Anti-GPVI-associated ITP: an acquired platelet disorder caused by autoantibody-mediated clearance of the GPVI/FcRγ-chain complex from the human platelet surface.  Blood. 2004;  104 1350-1355
• 6 Gawaz M. Role of platelets in coronary thrombosis and reperfusion of ischemic myocardium.  Cardiovasc Res. 2004;  61(3) 498-511
• 7 Lindemann S, Tolley N D, Eyre J R et al.. Integrins regulate the intracellular distribution of eukaryotic initiation factor 4E in platelets. A checkpoint for translational control.  J Biol Chem. 2001;  276(36) 33947-33951
• 8 Lindemann S, Tolley N D, Dixon D A et al.. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis.  J Cell Biol. 2001;  154(3) 485-490
• 9 Lindemann S W, Weyrich A S, Zimmerman G A. Signaling to translational control pathways: diversity in gene regulation in inflammatory and vascular cells.  Trends Cardiovasc Med. 2005;  15(1) 9-17
• 10 Penz S, Reininger A J, Brandl R et al.. Human atheromatous plaques stimulate thrombus formation by activating platelet glycoprotein VI.  FASEB J. 2005;  19(8) 898-909
• 11 Cosemans J M, Kuijpers M J, Lecut C et al.. Contribution of platelet glycoprotein VI to the thrombogenic effect of collagens in fibrous atherosclerotic lesions.  Atherosclerosis. 2005;  181(1) 19-27
• 12 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(8) 2117-2121
• 13 Samaha F F, 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(5) CR224-CR229
• 14 Clemetson K J, McGregor J L, James E et al.. Characterization of the platelet membrane glycoprotein abnormalities in Bernard-Soulier syndrome and comparison with normal by surface-labeling techniques and high-resolution two-dimensional gel electrophoresis.  J Clin Invest. 1982;  70(2) 304-311
• 15 Sugiyama T, Okuma M, Ushikubi F et al.. A novel platelet aggregating factor found in a patient with defective collagen-induced platelet aggregation and autoimmune thrombocytopenia.  Blood. 1987;  69(6) 1712-1720
• 16 Gawaz M, Neumann F J, Schomig A. Evaluation of platelet membrane glycoproteins in coronary artery disease: consequences for diagnosis and therapy.  Circulation. 1999;  99(1) E1-E11
• 17 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(8) 890-897
• 18 Massberg S, Konrad I, Bultmann A et al.. Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo.  FASEB J. 2004;  18(2) 397-399
• 19 Ikeda H, Takajo Y, Ichiki K et al.. Increased soluble form of P-selectin in patients with unstable angina.  Circulation. 1995;  92(7) 1693-1696
• 20 Gawaz M, Langer H, May A E. Platelets in inflammation and atherogenesis.  J Clin Invest. 2005;  115(12) 3378-3384
• 21 Massberg S, Gawaz M, Gruner S et al.. A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo.  J Exp Med. 2003;  197(1) 41-49
• 22 Ollikainen E, Mikkelsson J, Perola M et al.. Platelet membrane collagen receptor glycoprotein VI polymorphism is associated with coronary thrombosis and fatal myocardial infarction in middle-age men.  Atherosclerosis. 2004;  176(1) 95-99
• 23 Croft S A, Samani N J, Teare M D et al.. Novel platelet membrane glycoprotein VI dimorphism is a risk factor for myocardial infarction.  Circulation. 2001;  104 1459-1463
• 24 Joutsi-Korhonen L, Smethurst P A, Rankin A et al.. The low-frequency allele of the platelet collagen signalling receptor glycoprotein VI is associated with reduced functional responses and expression.  Blood. 2003;  101 4372-4379
• 25 Furihata K, Nugent D J, Kunicki T J. Influence of platelet collagen receptor polymorphisms on risk for arterial thrombosis.  Arch Pathol Lab Med. 2002;  126 305-309
• 26 Grüner S, Prostredna M, Aktas B et al.. Anti-glycoprotein VI treatment severely compromises hemostasis in mice with reduced alpha2beta1 levels or concomitant aspirin therapy.  Circulation. 2004;  110 2946-2951
• 27 Bultmann A, Herdeg C, Li Z et al.. Local delivery of soluble platelet collagen receptor glycoprotein VI inhibits thrombus formation in vivo.  Thromb Haemost. 2006;  95(5) 763-766