Diagnostic and Therapeutic Potentials of Platelet Glycoprotein VI

ABSTRACT

Platelets respond immediately to vascular injury by adhesion, aggregation, and thrombus formation. Disruption of the endothelial cell layer exposes extracellular matrix to the bloodstream. Collagen binding to platelet glycoprotein VI (GPVI) mediates the initial adhesion of the rolling platelet to the vascular wound. Signaling by GPVI leads to the onset of the platelet activation cascade that is finally crowned by a firm and shear-resistant integrin-based adhesive clot. Blockade of collagen binding to GPVI would prevent initial adhesion and further activation of the platelet and would have an enormous impact in antithrombotic therapy. Besides the therapeutical implication, radiolabeled GPVI gives us a valuable diagnostic means that may be used clinically for plaque imaging in the near future.

KEYWORDS

Platelet adhesion - glycoprotein VI - collagen - biomarker - cardiovascular disease

REFERENCES

• 1 Ginsberg M H, Loftus J, Plow E F. Platelets and the adhesion receptor superfamily.  Prog Clin Biol Res. 1988;  283 171-195
• 2 Shen Y, Romo G M, Dong J F et al.. Requirement of leucine-rich repeats of glycoprotein (GP) Ibalpha for shear-dependent and static binding of von Willebrand factor to the platelet membrane GP Ib-IX-V complex.  Blood. 2000;  95(3) 903-910
• 3 Kandzari D E, Goldschmidt-Clermont P J. Platelet polymorphisms and ischemic heart disease: moving beyond traditional risk factors.  J Am Coll Cardiol. 2001;  38(4) 1028-1032
• 4 Simon D I, Chen Z, Xu H et al.. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18).  J Exp Med. 2000;  192(2) 193-204
• 5 Glass C K, Witztum J L. Atherosclerosis. the road ahead.  Cell. 2001;  104(4) 503-516
• 6 Shah P K, Falk E, Badimon J J et al.. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture.  Circulation. 1995;  92(6) 1565-1569
• 7 Clemetson K J, McGregor J L, James E, Dechavanne M, Lüscher E F. 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
• 8 Moroi M, Jung S M, Okuma M, Shinmyozu K. A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion.  J Clin Invest. 1989;  84(5) 1440-1445
• 9 Moroi M, Jung S M. Platelet glycoprotein VI: its structure and function.  Thromb Res. 2004;  114(4) 221-233
• 10 Clemetson J M, Polgar J, Magnenat E, Wells T N, Clemetson K J. The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcalphaR and the natural killer receptors.  J Biol Chem. 1999;  274(41) 29019-29024
• 11 Locke D, Liu C, Peng X, Chen H, Kahn M L. Fc Rgamma—independent signaling by the platelet collagen receptor glycoprotein VI.  J Biol Chem. 2003;  278(17) 15441-15448
• 12 Takai T, Li M, Sylvestre D, Clynes R, Ravetch J V. FcR gamma chain deletion results in pleiotrophic effector cell defects.  Cell. 1994;  76(3) 519-529
• 13 Asselin J, Gibbins J M, Achison M et al.. A collagen-like peptide stimulates tyrosine phosphorylation of syk and phospholipase C gamma2 in platelets independent of the integrin alpha2beta1.  Blood. 1997;  89(4) 1235-1242
• 14 Poole A, Gibbins J M, Turner M et al.. The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen.  EMBO J. 1997;  16(9) 2333-2341
• 15 Ichinohe T, Takayama H, Ezumi Y et al.. Collagen-stimulated activation of Syk but not c-Src is severely compromised in human platelets lacking membrane glycoprotein VI.  J Biol Chem. 1997;  272(1) 63-68
• 16 Gross B S, Lee J R, Clements J L et al.. Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets.  J Biol Chem. 1999;  274(9) 5963-5971
• 17 Pasquet J M, Gross B, Quek L et al.. LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI.  Mol Cell Biol. 1999;  19(12) 8326-8334
• 18 Watson S P, Asazuma N, Atkinson B et al.. The role of ITAM- and ITIM-coupled receptors in platelet activation by collagen.  Thromb Haemost. 2001;  86(1) 276-288
• 19 Asazuma N, Wilde J I, Berlanga O et al.. Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin.  J Biol Chem. 2000;  275(43) 33427-33434
• 20 Locke D, Chen H, Liu Y, Liu C, Kahn M L. Lipid rafts orchestrate signaling by the platelet receptor glycoprotein VI.  J Biol Chem. 2002;  277(21) 18801-18809
• 21 Gibbins J M, Briddon S, Shutes A et al.. The p85 subunit of phosphatidylinositol 3-kinase associates with the Fc receptor γ-chain and linker for activator of T cells (LAT) in platelets stimulated by collagen and convulxin.  J Biol Chem. 1998;  273(51) 34437-34443
• 22 Watanabe N, Nakajima H, Suzuki H et al.. Functional phenotype of phosphoinositide 3-kinase p85α-null platelets characterized by an impaired response to GP VI stimulation.  Blood. 2003;  102(2) 541-548
• 23 Canobbio I, Stefanini L, Cipolla L et al.. Genetic evidence for a predominant role of PI3Kbeta catalytic activity in ITAM- and integrin-mediated signaling in platelets.  Blood. 2009;  114(10) 2193-2196
• 24 Kim S, Mangin P, Dangelmaier C et al.. Role of phosphoinositide 3-kinase beta in glycoprotein VI-mediated Akt activation in platelets.  J Biol Chem. 2009;  284(49) 33763-33772
• 25 Savage B, Almus-Jacobs F, Ruggeri Z M. Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow.  Cell. 1998;  94(5) 657-666
• 26 Sixma J J, van Zanten G H, Saelman E U et al.. Platelet adhesion to collagen.  Thromb Haemost. 1995;  74(1) 454-459
• 27 Sixma J J, van Zanten G H, Huizinga E G et al.. Platelet adhesion to collagen: an update.  Thromb Haemost. 1997;  78(1) 434-438
• 28 Jung S M, Moroi M. Platelets interact with soluble and insoluble collagens through characteristically different reactions.  J Biol Chem. 1998;  273(24) 14827-14837
• 29 Miura Y, Takahashi T, Jung S M, Moroi M. Analysis of the interaction of platelet collagen receptor glycoprotein VI (GPVI) with collagen. A dimeric form of GPVI, but not the monomeric form, shows affinity to fibrous collagen.  J Biol Chem. 2002;  277(48) 46197-46204
• 30 Polgár J, Clemetson J M, Kehrel B E et al.. Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor.  J Biol Chem. 1997;  272(21) 13576-13583
• 31 Jandrot-Perrus M, Lagrue A H, Okuma M, Bon C. Adhesion and activation of human platelets induced by convulxin involve glycoprotein VI and integrin α2β1.  J Biol Chem. 1997;  272(43) 27035-27041
• 32 Keely P J, Parise L V. The α2β1 integrin is a necessary co-receptor for collagen-induced activation of Syk and the subsequent phosphorylation of phospholipase Cgamma2 in platelets.  J Biol Chem. 1996;  271(43) 26668-26676
• 33 Trifiro E, Williams S A, Cheli Y et al.. The low-frequency isoform of platelet glycoprotein VIb attenuates ligand-mediated signal transduction but not receptor expression or ligand binding.  Blood. 2009;  114(9) 1893-1899
• 34 Joutsi-Korhonen L, Smethurst P A, Rankin A et al.. The low-frequency allele of the platelet collagen signaling receptor glycoprotein VI is associated with reduced functional responses and expression.  Blood. 2003;  101(11) 4372-4379
• 35 Watkins N A, O'Connor M N, Rankin A et al.. Definition of novel GP6 polymorphisms and major difference in haplotype frequencies between populations by a combination of in-depth exon resequencing and genotyping with tag single nucleotide polymorphisms.  J Thromb Haemost. 2006;  4(6) 1197-1205
• 36 Nurden A. GPVI: the inside story.  Blood. 2009;  114(9) 1723-1724
• 37 Dumont B, Lasne D, Rothschild C et al.. Absence of collagen-induced platelet activation caused by compound heterozygous GPVI mutations.  Blood. 2009;  114(9) 1900-1903
• 38 Hermans C, Wittevrongel C, Thys C, Smethurst P A, Van Geet C, Freson K. A compound heterozygous mutation in glycoprotein VI in a patient with a bleeding disorder.  J Thromb Haemost. 2009;  7(8) 1356-1363
• 39 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(2) 397-399
• 40 Massberg S, Gawaz M, Grüner 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
• 41 Nieswandt B, Brakebusch C, Bergmeier W et al.. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen.  EMBO J. 2001;  20(9) 2120-2130
• 42 Grüner S, Prostredna M, Koch M et al.. Relative antithrombotic effect of soluble GPVI dimer compared with anti-GPVI antibodies in mice.  Blood. 2005;  105(4) 1492-1499
• 43 Al-Tamimi M, Mu F T, Moroi M, Gardiner E E, Berndt M C, Andrews R K. Measuring soluble platelet glycoprotein VI in human plasma by ELISA.  Platelets. 2009;  20(3) 143-149
• 44 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(1) 193-200
• 45 Bigalke B, Stellos K, Geisler T et al.. Expression of platelet glycoprotein VI is associated with transient ischemic attack and stroke.  Eur J Neurol. 2010;  17 111-117
• 46 Ruggeri Z M. Platelets in atherothrombosis.  Nat Med. 2002;  8(11) 1227-1234
• 47 Remijn J A, Wu Y P, Jeninga E H et al.. Role of ADP receptor P2Y(12) in platelet adhesion and thrombus formation in flowing blood.  Arterioscler Thromb Vasc Biol. 2002;  22(4) 686-691
• 48 Kunapuli S P, Dorsam R T, Kim S, Quinton T M. Platelet purinergic receptors.  Curr Opin Pharmacol. 2003;  3(2) 175-180
• 49 Siljander P R, Munnix I C, Smethurst P A et al.. Platelet receptor interplay regulates collagen-induced thrombus formation in flowing human blood.  Blood. 2004;  103(4) 1333-1341
• 50 Zwaal R F, Schroit A J. Pathophysiologic implications of membrane phospholipid asymmetry in blood cells.  Blood. 1997;  89(4) 1121-1132
• 51 Lindemann S, Tolley N D, Eyre J R, Kraiss L W, Mahoney T M, Weyrich A S. 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
• 52 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
• 53 Barnes M J, Farndale R W. Collagens and atherosclerosis.  Exp Gerontol. 1999;  34(4) 513-525
• 54 Badimon L. Atherosclerosis and thrombosis: lessons from animal models.  Thromb Haemost. 2001;  86(1) 356-365
• 55 Galt S W, Lindemann S, Medd D et al.. Differential regulation of matrix metalloproteinase-9 by monocytes adherent to collagen and platelets.  Circ Res. 2001;  89(6) 509-516
• 56 Galt S W, Lindemann S, Allen L et al.. Outside-in signals delivered by matrix metalloproteinase-1 regulate platelet function.  Circ Res. 2002;  90(10) 1093-1099
• 57 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
• 58 Cabeza N, Li Z, Schulz C et al.. Surface expression of collagen receptor Fc receptor-γ/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
• 59 Heeschen C, Dimmeler S, Hamm C W CAPTURE Study Investigators et al. Soluble CD40 ligand in acute coronary syndromes.  N Engl J Med. 2003;  348(12) 1104-1111
• 60 Bigalke B, Lindemann S, Ehlers R et al.. Expression of platelet collagen receptor glycoprotein VI is associated with acute coronary syndrome.  Eur Heart J. 2006;  27(18) 2165-2169
• 61 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(2) 397-399
• 62 Gawaz M, Konrad I, Hauser A I et al.. Non-invasive imaging of glycoprotein VI binding to injured arterial lesions.  Thromb Haemost. 2005;  93(5) 910-913
• 63 Bültmann 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
• 64 Bigalke B, Stellos K, Weig H J et al.. Regulation of platelet glycoprotein VI (GPVI) surface expression and of soluble GPVI in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS).  Basic Res Cardiol. 2009;  104(3) 352-357
• 65 Bigalke B, Stellos K, Stakos D et al.. Influence of platelet count on the expression of platelet collagen receptor glycoprotein VI (GPVI) in patients with acute coronary syndrome.  Thromb Haemost. 2009;  101(5) 911-915
• 66 Bigalke B, Stellos K, Geisler T et al.. Glycoprotein VI as a prognostic biomarker for cardiovascular death in patients with symptomatic coronary artery disease.  Clin Res Cardiol. 2010;  , January 5 (Epub ahead of print)
• 67 Bigalke B, Haap M, Stellos K et al.. Platelet glycoprotein VI (GPVI) for early identification of acute coronary syndrome in patients with chest pain.  Thromb Res. 2010;  , January 30 (Epub ahead of print)
• 68 Bigalke B, Stellos K, Geisler T et al.. Glycoprotein VI for diagnosis of acute coronary syndrome when the ECG is ambiguous.  Int J Cardiol. 2010;  , January 11 (Epub ahead of print)