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Monocyte–Platelets Aggregates as Cellular Biomarker of Endothelium-Dependent Coronary Vasomotor Dysfunction in Patients with Coronary Artery Disease

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Abstract

Monocyte–platelet aggregates (MPA) are increased in patients with acute coronary syndrome. We investigated whether MPA are associated with the presence of functionally significant coronary stenoses or with coronary arterial endothelial dysfunction. One hundred forty five patients undergoing elective coronary angiography were prospectively enrolled. Functional significance of coronary stenosis was assessed by fractional flow reserve (FFR). Thirty randomly selected patients underwent pacing protocol to evaluate Coronary endothelium-dependent vasomotor function (CVF). Whole blood was drawn to evaluate MPA. In patients with FFR ≤ 0.8 (FFRpos, n = 75), MPA did not significantly differ from FFR >0.8 patients (FFRneg, n = 70) (38.1 % [25.7–56.6] vs 34.0 % [20.5–49.9], p = 0.08). CVF was similar in FFRpos and FFRneg patients (percent vessel diameter change, %VDC = 7.19 % [6.01–10.9] vs 8.0 % [0.81–9.80], p = 0.78). Yet, patients with abnormal CVF showed higher MPA as compared to patients with preserved CVF (28.3 % [28.8–53.4] vs 20.5 % [17.0–32.9], p = 0.01). Moreover, MPA was inversely correlated with %VDC (R 2 = 0.26, p < 0.01). MPA levels are significantly higher in patients with abnormal coronary vasomotor function regardless of the presence of functionally significant coronary stenosis.

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References

  1. Ruggeri, Z. M. (2002). Platelets in atherothrombosis. Nature Medicine, 8(11), 1227–1234. doi:10.1038/nm1102-1227.

    Article  CAS  PubMed  Google Scholar 

  2. Davi, G., & Patrono, C. (2007). Platelet activation and atherothrombosis. The New England Journal of Medicine, 357(24), 2482–2494. doi:10.1056/NEJMra071014.

    Article  CAS  PubMed  Google Scholar 

  3. Danenberg, H. D., Kantak, N., Grad, E., Swaminathan, R. V., Lotan, C., & Edelman, E. R. (2007). C-reactive protein promotes monocyte–platelet aggregation: an additional link to the inflammatory-thrombotic intricacy. European Journal of Haematology, 78(3), 246–252. doi:10.1111/j.1600-0609.2006.00808.x.

    Article  CAS  PubMed  Google Scholar 

  4. Kalsch, T., Elmas, E., Nguyen, X. D., Suvajac, N., Kluter, H., Borggrefe, M., & Dempfle, C. E. (2007). Endotoxin-induced effects on platelets and monocytes in an in vivo model of inflammation. Basic Research in Cardiology, 102(5), 460–466. doi:10.1007/s00395-007-0667-y.

    Article  PubMed  Google Scholar 

  5. Passacquale, G., Vamadevan, P., Pereira, L., Hamid, C., Corrigall, V., & Ferro, A. (2011). Monocyte–platelet interaction induces a pro-inflammatory phenotype in circulating monocytes. PloS one, 6(10), e25595. doi:10.1371/journal.pone.0025595.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Furman, M. I., Benoit, S. E., Barnard, M. R., Valeri, C. R., Borbone, M. L., Becker, R. C., Hechtman, H. B., & Michelson, A. D. (1998). Increased platelet reactivity and circulating monocyte–platelet aggregates in patients with stable coronary artery disease. Journal of the American College of Cardiology, 31(2), 352–358.

    Article  CAS  PubMed  Google Scholar 

  7. Hamilos, M., Sarma, J., Ostojic, M., Cuisset, T., Sarno, G., Melikian, N., Ntalianis, A., Muller, O., Barbato, E., Beleslin, B., Sagic, D., De Bruyne, B., Bartunek, J., & Wijns, W. (2008). Interference of drug-eluting stents with endothelium-dependent coronary vasomotion: evidence for device-specific responses. Circulation. Cardiovascular Interventions, 1(3), 193–200. doi:10.1161/CIRCINTERVENTIONS.108.797928.

    Article  PubMed  Google Scholar 

  8. Gordon, J. B., Ganz, P., Nabel, E. G., Fish, R. D., Zebede, J., Mudge, G. H., Alexander, R. W., & Selwyn, A. P. (1989). Atherosclerosis influences the vasomotor response of epicardial coronary arteries to exercise. The Journal of Clinical Investigation, 83(6), 1946–1952. doi:10.1172/JCI114103.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Robinson, S. D., Harding, S. A., Cummins, P., Din, J. N., Sarma, J., Davidson, I., Fox, K. A., Boon, N. A., & Newby, D. E. (2006). Functional interplay between platelet activation and endothelial dysfunction in patients with coronary heart disease. Platelets, 17(3), 158–162. doi:10.1080/17476930500454514.

    Article  CAS  PubMed  Google Scholar 

  10. Chatzizisis, Y. S., Coskun, A. U., Jonas, M., Edelman, E. R., Feldman, C. L., & Stone, P. H. (2007). Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. Journal of the American College of Cardiology, 49(25), 2379–2393. doi:10.1016/j.jacc.2007.02.059.

    Article  CAS  PubMed  Google Scholar 

  11. Mangiacapra, F., & Barbato, E. (2013). Clinical implications of platelet–vessel interaction. Journal of Cardiovascular Translational Research, 6(3), 310–315. doi:10.1007/s12265-012-9441-0.

    Article  PubMed  Google Scholar 

  12. Muller, O., Bartunek, J., Hamilos, M., Berza, C. T., Mangiacapra, F., Ntalianis, A., Vercruysse, K., Duby, C., Wijns, W., De Bruyne, B., Heyndrickx, G. R., Vanderheyden, M., Holz, J. B., & Barbato, E. (2013). von Willebrand factor inhibition improves endothelial function in patients with stable angina. Journal of Cardiovascular Translational Research, 6(3), 364–370. doi:10.1007/s12265-012-9422-3.

    Article  PubMed  Google Scholar 

  13. Mayadas, T. N., Johnson, R. C., Rayburn, H., Hynes, R. O., & Wagner, D. D. (1993). Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell, 74(3), 541–554.

    Article  CAS  PubMed  Google Scholar 

  14. Massberg, S., Brand, K., Gruner, S., Page, S., Muller, E., Muller, I., Bergmeier, W., Richter, T., Lorenz, M., Konrad, I., Nieswandt, B., & Gawaz, M. (2002). A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. The Journal of Experimental Medicine, 196(7), 887–896.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Theilmeier, G., Michiels, C., Spaepen, E., Vreys, I., Collen, D., Vermylen, J., & Hoylaerts, M. F. (2002). Endothelial von Willebrand factor recruits platelets to atherosclerosis-prone sites in response to hypercholesterolemia. Blood, 99(12), 4486–4493.

    Article  CAS  PubMed  Google Scholar 

  16. Diodati, J. G., Dakak, N., Gilligan, D. M., & Quyyumi, A. A. (1998). Effect of atherosclerosis on endothelium-dependent inhibition of platelet activation in humans. Circulation, 98(1), 17–24.

    Article  CAS  PubMed  Google Scholar 

  17. Rosenblum, W. I. (1997). Platelet adhesion and aggregation without endothelial denudation or exposure of basal lamina and/or collagen. Journal of Vascular Research, 34(6), 409–417.

    Article  CAS  PubMed  Google Scholar 

  18. Bogaty, P., Brecker, S. J., White, S. E., Stevenson, R. N., El-Tamimi, H., Balcon, R., & Maseri, A. (1993). Comparison of coronary angiographic findings in acute and chronic first presentation of ischemic heart disease. Circulation, 87(6), 1938–1946.

    Article  CAS  PubMed  Google Scholar 

  19. Pijls, N. H., De Bruyne, B., Peels, K., Van Der Voort, P. H., Bonnier, H. J., Bartunek, J. K. J. J., & Koolen, J. J. (1996). Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. The New England Journal of Medicine, 334(26), 1703–1708. doi:10.1056/NEJM199606273342604.

    Article  CAS  PubMed  Google Scholar 

  20. De Bruyne, B., Pijls, N. H., Bartunek, J., Kulecki, K., Bech, J. W., De Winter, H., Van Crombrugge, P., Heyndrickx, G. R., & Wijns, W. (2001). Fractional flow reserve in patients with prior myocardial infarction. Circulation, 104(2), 157–162.

    Article  PubMed  Google Scholar 

  21. De Bruyne, B., Pijls, N. H., Barbato, E., Bartunek, J., Bech, J. W., Wijns, W., & Heyndrickx, G. R. (2003). Intracoronary and intravenous adenosine 5′-triphosphate, adenosine, papaverine, and contrast medium to assess fractional flow reserve in humans. Circulation, 107(14), 1877–1883. doi:10.1161/01.CIR.0000061950.24940.88.

    Article  PubMed  Google Scholar 

  22. Galassi, A. R., Tomasello, S. D., Crea, F., Costanzo, L., Campisano, M. B., Marza, F., & Tamburino, C. (2012). Transient impairment of vasomotion function after successful chronic total occlusion recanalization. Journal of the American College of Cardiology, 59(8), 711–718. doi:10.1016/j.jacc.2011.10.894.

    Article  PubMed  Google Scholar 

  23. Hamilos, M. I., Ostojic, M., Beleslin, B., Sagic, D., Mangovski, L., Stojkovic, S., Nedeljkovic, M., Orlic, D., Milosavljevic, B., Topic, D., Karanovic, N., & Wijns, W. (2008). Differential effects of drug-eluting stents on local endothelium-dependent coronary vasomotion. Journal of the American College of Cardiology, 51(22), 2123–2129. doi:10.1016/j.jacc.2007.12.059.

    Article  CAS  PubMed  Google Scholar 

  24. Harding, S. A., Din, J. N., Sarma, J., Jessop, A., Weatherall, M., Fox, K. A., & Newby, D. E. (2007). Flow cytometric analysis of circulating platelet–monocyte aggregates in whole blood: methodological considerations. Thrombosis and Haemostasis, 98(2), 451–456.

    CAS  PubMed  Google Scholar 

  25. Lusis, A. J. (2000). Atherosclerosis. Nature, 407(6801), 233–241. doi:10.1038/35025203.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Egan, K. M., Wang, M., Fries, S., Lucitt, M. B., Zukas, A. M., Pure, E., Lawson, J. A., & FitzGerald, G. A. (2005). Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonism. Circulation, 111(3), 334–342. doi:10.1161/01.CIR.0000153386.95356.78.

    Article  CAS  PubMed  Google Scholar 

  27. Pratico, D., Cyrus, T., Li, H., & FitzGerald, G. A. (2000). Endogenous biosynthesis of thromboxane and prostacyclin in 2 distinct murine models of atherosclerosis. Blood, 96(12), 3823–3826.

    CAS  PubMed  Google Scholar 

  28. Dong, Z. M., Chapman, S. M., Brown, A. A., Frenette, P. S., Hynes, R. O., & Wagner, D. D. (1998). The combined role of P- and E-selectins in atherosclerosis. The Journal of Clinical Investigation, 102(1), 145–152. doi:10.1172/JCI3001.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Dong, Z. M., Brown, A. A., & Wagner, D. D. (2000). Prominent role of P-selectin in the development of advanced atherosclerosis in ApoE-deficient mice. Circulation, 101(19), 2290–2295.

    Article  CAS  PubMed  Google Scholar 

  30. Burger, P. C., & Wagner, D. D. (2003). Platelet P-selectin facilitates atherosclerotic lesion development. Blood, 101(7), 2661–2666. doi:10.1182/blood-2002-07-2209.

    Article  CAS  PubMed  Google Scholar 

  31. Lindemann, S., Tolley, N. D., Dixon, D. A., McIntyre, T. M., Prescott, S. M., Zimmerman, G. A., & Weyrich, A. S. (2001). Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. The Journal of Cell Biology, 154(3), 485–490. doi:10.1083/jcb.200105058.

    Article  CAS  PubMed  Google Scholar 

  32. McEver, R. P. (2001). Adhesive interactions of leukocytes, platelets, and the vessel wall during hemostasis and inflammation. Thrombosis and Haemostasis, 86(3), 746–756.

    CAS  PubMed  Google Scholar 

  33. Henn, V., Slupsky, J. R., Grafe, M., Anagnostopoulos, I., Forster, R., Muller-Berghaus, G., & Kroczek, R. A. (1998). CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature, 391(6667), 591–594. doi:10.1038/35393.

    Article  CAS  PubMed  Google Scholar 

  34. Subramaniam, M., Saffaripour, S., Watson, S. R., Mayadas, T. N., Hynes, R. O., & Wagner, D. D. (1995). Reduced recruitment of inflammatory cells in a contact hypersensitivity response in P-selectin-deficient mice. The Journal of Experimental Medicine, 181(6), 2277–2282.

    Article  CAS  PubMed  Google Scholar 

  35. Sarma, J., Laan, C. A., Alam, S., Jha, A., Fox, K. A., & Dransfield, I. (2002). Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation, 105(18), 2166–2171.

    Article  PubMed  Google Scholar 

  36. De Bruyne, B., Pijls, N. H., Kalesan, B., Barbato, E., Tonino, P. A., Piroth, Z., Jagic, N., Mobius-Winkler, S., Rioufol, G., Witt, N., Kala, P., MacCarthy, P., Engstrom, T., Oldroyd, K. G., Mavromatis, K., Manoharan, G., Verlee, P., Frobert, O., Curzen, N., Johnson, J. B., Juni, P., & Fearon, W. F. (2012). Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. The New England Journal of Medicine, 367(11), 991–1001. doi:10.1056/NEJMoa1205361.

    Article  PubMed  Google Scholar 

  37. Gremmel, T., Kopp, C. W., Seidinger, D., Giurgea, G. A., Koppensteiner, R., Steiner, S., & Panzer, S. (2009). The formation of monocyte-platelet aggregates is independent of on-treatment residual agonists'-inducible platelet reactivity. Atherosclerosis, 207(2), 608–613. doi:10.1016/j.atherosclerosis.2009.05.037.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work has been supported by the Meijer Lavino Foundation for Cardiac Research, Aalst, Belgium.

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Authors and Affiliations

  1. Cardiovascular Center Aalst, OLV Hospital, Moorselbaan164, 9300, Aalst, Belgium

    Luigi Di Serafino, Jaydeep Sarma, Karen Dierickx, Ioannis Ntarladimas, Stylianos A. Pyxaras, Leen Delrue, Bernard De Bruyne, William Wijns, Emanuele Barbato & Jozef Bartunek

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  1. Luigi Di Serafino
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  2. Jaydeep Sarma
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  3. Karen Dierickx
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Correspondence to Jozef Bartunek.

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Associate Editor Dominick Angiolillo

Luigi Di Serafino and Jaydeep Sarma contributed equally to this work.

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Di Serafino, L., Sarma, J., Dierickx, K. et al. Monocyte–Platelets Aggregates as Cellular Biomarker of Endothelium-Dependent Coronary Vasomotor Dysfunction in Patients with Coronary Artery Disease. J. of Cardiovasc. Trans. Res. 7, 1–8 (2014). https://doi.org/10.1007/s12265-013-9520-x

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