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Regulation of platelet glycoprotein VI (GPVI) surface expression and of soluble GPVI in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS)

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Abstract

Background

The platelet collagen receptor glycoprotein VI (GPVI) mediates platelet adhesion to subendothelial matrix and thrombus formation in acute coronary syndrome (ACS). This study examined patients with both ACS and stable coronary artery disease (CAD), which presented with atrial fibrillation (AF) and sinus rhythm (SR).

Methods and results

We evaluated 992 patients with acute or stable CAD, and determined platelet surface expression of GPVI using flow cytometry. Seventy-eight patients presented with nonvalvular persistent AF. After 1:1 propensity score matching 156 matched cases with 78 pairs were obtained. Patients with AF and ACS showed a significantly decreased GPVI expression compared to patients with ACS and SR, whereas patients with stable angina pectoris (SA) presented with low level activation and no significant difference between SR and AF [mean fluorescence intensity (MFI) for ACS (SR Vs. AF): 20 ± 6.3 Vs. 17.7 ± 4.4; P = 0.023; SA (SR Vs. AF): 18.8 ± 9.4 Vs. 18.1 ± 6.1; P = 0.649]. In contrast, soluble GPVI was increased in ACS and AF accordingly [plasma GPVI (ng/ml) for ACS (SR Vs. AF): 1.4 ± 0.8 Vs. 1.9 ± 1.1; P = 0.038; SA (SR Vs. AF): 0.9 ± 0.4 Vs. 1.1 ± 0.5; P = 0.127].

Conclusion

Platelet GPVI surface expression is decreased in patients with AF and ACS compared to patients with SR and ACS. Nonvalvular AF is related to indices of chronic platelet activation and might be responsible for a down-regulation of GPVI receptor density on platelets, while soluble GPVI was increased in ACS and AF accordingly.

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References

  1. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE 2nd, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B (2007) ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: 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 116:e148–e3044

    Article  PubMed  Google Scholar 

  2. Andrews RK, Karunakaran D, Gardiner EE, Berndt MC (2007) Platelet receptor proteolysis: a mechanism for downregulating platelet reactivity. Arterioscler Thromb Vasc Biol 27:1511–1520

    Article  PubMed  CAS  Google Scholar 

  3. Bigalke B, Geisler T, Stellos K, Langer H, Daub K, Kremmer E, Seizer P, May AE, Lindemann S, Gawaz M (2008) Platelet collagen receptor glycoprotein VI as a possible novel indicator for the acute coronary syndrome. Am Heart J 156:193–200

    Article  PubMed  CAS  Google Scholar 

  4. Bigalke B, Lindemann S, Ehlers R, Seizer P, Daub K, Langer H, Schonberger T, Kremmer E, Siegel-Axel D, May AE, Gawaz M (2006) Expression of platelet collagen receptor VI is associated with acute coronary syndrome. Eur Heart J 27:2165–2169

    Article  PubMed  CAS  Google Scholar 

  5. Berndt MC, Karunakaran D, Gardiner EE, Andrews RK (2007) Programmed autologous cleavage of platelet receptors. J Thromb Haemost 5(Suppl 1):212–219

    Article  PubMed  CAS  Google Scholar 

  6. Blann AD (2004) Angiogenesis and platelets: the clot thinkens further. Cardiovasc Res 63:192–193

    Article  PubMed  CAS  Google Scholar 

  7. Blann AD, Choudhury A, Freestone B, Patel J, Lip GY (2008) Soluble CD40 ligand and atrial fibrillation: relationship to platelet activation, and endothelial damage/dysfunction. Int J Cardiol 127:135–137

    Article  PubMed  CAS  Google Scholar 

  8. Bolin RB, Cheney BA, Simpliciano OA, Peck CC (1980) In vitro evaluation of platelets stored in CDP-adenine formulations. Transfusion 20:409–418

    Article  PubMed  CAS  Google Scholar 

  9. Choudhury A, Chung I, Blann AD, Lip GY (2007) Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy. Chest 131:809–815

    Article  PubMed  CAS  Google Scholar 

  10. Choudhury A, Chung I, Blann AD, Lip GYH (2007) Platelet surface CD62P and CD63, mean platelet volume, and soluble/platelet p-selectin as indexes of platelet function in atrial fibrillation. J Am Coll Cardiol 49:1957–1964

    Article  PubMed  CAS  Google Scholar 

  11. Conway DS, Pearce LA, Chin BS, Hart RG, Lip GY (2002) Plasma von Willebrand factor and soluble p-selectin as indices of endothelial damage and platelet activation in 1,321 patients with non-valvular atrial fibrillation: relationship to stroke risk factors. Circulation 106:1962–1967

    Article  PubMed  CAS  Google Scholar 

  12. D’Agostino RB Jr (1998) Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17:2265–2281

    Article  PubMed  Google Scholar 

  13. Gardiner EE, Arthur JF, Kahn ML, Berndt MC, Andrews RK (2004) Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase. Blood 104:3611–3617

    Article  PubMed  CAS  Google Scholar 

  14. Gardiner EE, Karunakaran D, Shen Y, Arthur JF, Andrews RK, Berndt MC (2007) Controlled shedding of platelet glycoprotein (GP)VI and GPIb-IX-V by ADAM family metalloproteinases. J Thromb Haemost 5:1530–1537

    Article  PubMed  CAS  Google Scholar 

  15. Goto S, Tamura N, Handa S, Arai M, Kodama K, Takayama H (2002) Involvement of glycoprotein VI in platelet thrombus formation on both collagen and von Willebrand factor surfaces under flow conditions. Circulation 106:266–272

    Article  PubMed  CAS  Google Scholar 

  16. Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T (1997) Emergency room triage with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 337:1648–1653

    Article  PubMed  CAS  Google Scholar 

  17. Kälsch T, Elmas E, Nguyen XD, Suvajac N, Klüter H, Borggrefe M, Dempfle CE (2007) Endotoxin-induced effects on platelets and monocytes in an in vivo model of inflammation. Basic Res Cardiol 102:460–466

    Article  PubMed  Google Scholar 

  18. Laske C, Leyhe T, Stransky E, Eschweiler GW, Bueltmann A, Langer H, Stellos K, Gawaz M (2008) Association of platelet-derived soluble glycoprotein VI in plasma with Alzheimer’s disease. J Psychiatr Res 42:746–751

    Article  PubMed  Google Scholar 

  19. Lip GYH (2003) The prothrombotic state in atrial fibrillation: the atrium, the endothelium… and tissue factor? Thromb Res 111:133–135

    Article  PubMed  CAS  Google Scholar 

  20. Lip GY, Tse HF (2007) Management of atrial fibrillation. Lancet 370:604–618

    Article  PubMed  Google Scholar 

  21. Massberg S, Konrad I, Bultmann A, Schulz C, Münch G, Peluso M, Lorenz M, Schneider S, Besta F, Müller I, Hu B, Langer H, Kremmer E, Rudelius M, Heinzmann U, Ungerer M, Gawaz M (2004) Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo. FASEB J 18:397–399

    PubMed  CAS  Google Scholar 

  22. Nieswandt B, Watson SP (2003) Platelet-collagen interaction: is GPVI the central receptor? Blood 102:449–461

    Article  PubMed  CAS  Google Scholar 

  23. Rabie T, Varga-Szabo D, Bender M, Pozgaj R, Lanza F, Saito T, Watson SP, Nieswandt B (2007) Diverging signaling events control the pathway of GPVI down-regulation in vivo. Blood 110:529–535

    Article  PubMed  CAS  Google Scholar 

  24. Rosenbaum PR, Rubin DB (1983) The central role of the propensity score in observational studies for causal effects. Biometrika 70:41–55

    Article  Google Scholar 

  25. Rudner LM, Peyton J (2006) Consider propensity scores to compare treatments. PARE 11:1–9

    Google Scholar 

  26. Schulz C, Penz S, Hoffmann C, Langer H, Gillitzer A, Schneider S, Brandl R, Seidl S, Massberg S, Pichler B, Kremmer E, Stellos K, Schönberger T, Siess W, Gawaz M (2008) Platelet GPVI binds to collagenous structures in the core region of human atheromatous plaque and is critical for atheroprogression in vivo. Basic Res Cardiol 103:356–367

    Article  PubMed  CAS  Google Scholar 

  27. Steg PG, Bhatt DL, Wilson PW, D’Agostino R Sr, Ohman EM, Röther J, Liau CS, Hirsch AT, Mas JL, Ikeda Y, Pencina MJ, Goto S (2007) One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA 297: 1197–1206

    Article  PubMed  CAS  Google Scholar 

  28. Stephens G, Yan Y, Jandrot-Perrus M, Villeval JL, Clemetson KJ, Phillips DR (2005) Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen. Blood 105:186–191

    Article  PubMed  CAS  Google Scholar 

  29. Yip HK, Chang LT, Sun CK, Yang CH, Hung WC, Hang CL, Wu CJ, Chua S, Yeh KH, Chang HW (2006) Platelet activation in patients with chronic nonvalvular atrial fibrillation. Int Heart J 47:371–379

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The study was supported by grants of Deutsche Forschungsgemeinschaft (MA2186/3-1&GK794 to M.G. and Li 849/3-1 to S.L.), Karl-und-Lore-Klein-Stiftung (D.30.08886), Karl-Kuhn-Stiftung and Wilhelm-Sanders-Stiftung (Nr. 2003.0601), and AKF-Program (No. 231-0-0).

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Correspondence to Meinrad Gawaz MD.

Additional information

Returned for 1. Revision: 3 July 2008 1. Revision received: 6 October 2008

Returned for 2. Revision: 22 October 2008 2. Revision received: 9 December 2008

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Bigalke, B., Stellos, K., Weig, HJ. 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 104, 352–357 (2009). https://doi.org/10.1007/s00395-009-0779-7

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  • DOI: https://doi.org/10.1007/s00395-009-0779-7

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