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Platelet and monocyte activity markers and mediators of inflammation in Takotsubo cardiomyopathy

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Abstract

Patients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- and monocyte-activity markers in patients with TC and MI for significant differences. Clinical data of patients with TC (n = 16) and acute MI (n = 16) were obtained. Serial blood samples were taken at the time of hospital admission (t 0), after 2–4 days (t 1) and after 4–7 weeks (t 2), respectively. Plasma concentrations of interleukin (IL)-6, IL-7, soluble CD40 ligand (sCD40L), and monocyte chemotactic protein 1 (MCP-1) were determined with an ELISA. Tissue factor binding on monocytes, platelet-activation marker CD62P, platelet CD40-ligand (CD40L), and platelet-monocyte aggregates were measured using flow cytometry. Expression of CD62P on platelets and IL-6 plasma levels were significantly lower in patients with TC compared to MI at the time of hospital admission. IL-7 plasma levels were significantly elevated in patients with TC compared to patients with MI at 2–4 days after hospital admission. No significant differences were observed concerning sCD40L and MCP-1 plasma levels, tissue factor binding on monocytes, CD40L expression on platelets, and platelet-monocyte aggregates at any point in time. Our results indicate that inflammatory mediators and platelet-activity markers contribute to the differences in the pathogenesis of MI and TC.

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References

  1. Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC (2005) Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 352:539–548

    Article  PubMed  CAS  Google Scholar 

  2. Ueyama T, Yamamoto Y, Ueda K, Kawabe T, Hano T, Ito T, Tsuruo Y, Ichinose M, Yoshida K-i (2010) Cardiac and vascular gene profiles in an animal model of Takotsubo cardiomyopathy. Heart Vessels. doi:10.1007/s00380-010-0070-8

  3. Ruggeri ZM (2002) Platelets in atherothrombosis. Nat Med 8:1227–1234

    Article  PubMed  CAS  Google Scholar 

  4. May AE, Kälsch T, Massberg S, Herouy Y, Schmidt R, Gawaz M (2002) Engagement of glycoprotein iib/iiia (alpha(iib)beta3) on platelets upregulates CD40 l and triggers CD40 l-dependent matrix degradation by endothelial cells. Circulation 106:2111–2117

    Article  PubMed  CAS  Google Scholar 

  5. Kayrak M, Bacaksiz A, Ulgen MS, Vatankulu MA, Zengin K, Ayhan SS, Basarali MK, Buyukbas S, Kiyici A (2010) Plasma concentrations of soluble CD40 ligand in smokers with acute myocardial infarction: a pilot study. Heart Vessels. doi:10.1007/s00380-010-0036-x

  6. Setianto BY, Hartopo AB, Gharini PP, Anggrahini DW, Irawan B (2010) Circulating soluble CD40 ligand mediates the interaction between neutrophils and platelets in acute coronary syndrome. Heart Vessels 25:282–287

    Article  PubMed  Google Scholar 

  7. Chakrabarti S, Varghese S, Vitseva O, Tanriverdi K, Freedman JE (2005) Cd40 ligand influences platelet release of reactive oxygen intermediates. Arterioscler Thromb Vasc Biol 25:2428–2434

    Article  PubMed  CAS  Google Scholar 

  8. Sanguigni V, Ferro D, Pignatelli P, Del Ben M, Nadia T, Saliola M, Sorge R, Violi F (2005) Cd40 ligand enhances monocyte tissue factor expression and thrombin generation via oxidative stress in patients with hypercholesterolemia. J Am Coll Cardiol 45:35–42

    Article  PubMed  CAS  Google Scholar 

  9. Mach F, Schonbeck U, Sukhova GK, Bourcier T, Bonnefoy JY, Pober JS, Libby P (1997) Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40-CD40 ligand signaling in atherosclerosis. Proc Natl Acad Sci USA 94:1931–1936

    Article  PubMed  CAS  Google Scholar 

  10. Galkina E, Ley K (2007) Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol 27:2292–2301

    Article  PubMed  CAS  Google Scholar 

  11. Raymond RJ, Dehmer GJ, Theoharides TC, Deliargyris EN (2001) Elevated interleukin-6 levels in patients with asymptomatic left ventricular systolic dysfunction. Am Heart J 141:435–438

    Article  PubMed  CAS  Google Scholar 

  12. Damås JK, Waehre T, Yndestad A, Otterdal K, Hognestad A, Solum NO, Gullestad L, Froland SS, Aukrust P (2003) Interleukin-7-mediated inflammation in unstable angina: possible role of chemokines and platelets. Circulation 107:2670–2676

    Article  PubMed  Google Scholar 

  13. Prasad A, Lerman A, Rihal CS (2008) Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J 155:408–417

    Article  PubMed  Google Scholar 

  14. Madhavan M, Borlaug BA, Lerman A, Rihal CS, Prasad A (2009) Stress hormone and circulating biomarker profile of apical ballooning syndrome (Takotsubo cardiomyopathy): insights into the clinical significance of b-type natriuretic peptide and troponin levels. Heart 95:1436–1441

    Article  PubMed  CAS  Google Scholar 

  15. Trip MD, Cats VM, van Capelle FJ, Vreeken J (1990) Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 322:1549–1554

    Article  PubMed  CAS  Google Scholar 

  16. Sarma J, Laan CA, Alam S, Jha A, Fox KA, Dransfield I (2002) Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 105:2166–2171

    Article  PubMed  Google Scholar 

  17. Kälsch T, Nguyen XD, Elmas E, Grebert N, Suselbeck T, Kluter H, Borggrefe M, Dempfle CE (2006) Coagulation activation and expression of CD40 ligand on platelets upon in vitro lipopolysaccharide-challenge in patients with unstable angina. Int J Cardiol 111:217–223

    Article  PubMed  Google Scholar 

  18. Yip HK, Chang LT, Sun CK, Chen MC, Yang CH, Hung WC, Hsieh YK, Fang CY, Hang CL, Wu CJ, Chang HW (2006) Platelet activity is a biomarker of cardiac necrosis and predictive of untoward clinical outcomes in patients with acute myocardial infarction undergoing primary coronary stenting. Circ J 70:31–36

    Article  PubMed  Google Scholar 

  19. Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V (2000) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148:209–214

    Article  PubMed  CAS  Google Scholar 

  20. Biasucci LM, Liuzzo G, Fantuzzi G, Caligiuri G, Rebuzzi AG, Ginnetti F, Dinarello CA, Maseri A (1999) Increasing levels of interleukin (IL)-1ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events. Circulation 99:2079–2084

    PubMed  CAS  Google Scholar 

  21. Buratti T, Ricevuti G, Pechlaner C, Joannidis M, Wiedermann FJ, Gritti D, Herold M, Wiedermann CJ (2001) Plasma levels of procalcitonin and interleukin-6 in acute myocardial infarction. Inflammation 25:97–100

    Article  PubMed  CAS  Google Scholar 

  22. Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E (2006) Apical ballooning syndrome or Takotsubo cardiomyopathy: a systematic review. Eur Heart J 27:1523–1529

    Article  PubMed  Google Scholar 

  23. Heggemann F, Weiss C, Hamm K, Kaden J, Suselbeck T, Papavassiliu T, Borggrefe M, Haghi D (2009) Global and regional myocardial function quantification by two-dimensional strain in Takotsubo cardiomyopathy. Eur J Echocardiogr 10:760–764

    Article  PubMed  Google Scholar 

  24. Tsutamoto T, Hisanaga T, Wada A, Maeda K, Ohnishi M, Fukai D, Mabuchi N, Sawaki M, Kinoshita M (1998) Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol 31:391–398

    Article  PubMed  CAS  Google Scholar 

  25. Plenz G, Song ZF, Reichenberg S, Tjan TD, Robenek H, Deng MC (1998) Left-ventricular expression of interleukin-6 messenger-RNA higher in idiopathic dilated than in ischemic cardiomyopathy. Thorac Cardiovasc Surg 46:213–216

    Article  PubMed  CAS  Google Scholar 

  26. Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL (1992) Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257:387–389

    Article  PubMed  CAS  Google Scholar 

  27. Fry TJ, Mackall CL (2001) Interleukin-7: master regulator of peripheral t-cell homeostasis? Trends Immunol 22:564–571

    Article  PubMed  CAS  Google Scholar 

  28. Li L, Masucci MG, Levitsky V (2000) Effect of interleukin-7 on the in vitro development and maturation of monocyte derived human dendritic cells. Scand J Immunol 51:361–371

    Article  PubMed  CAS  Google Scholar 

  29. Furuno T, Yamasaki F, Yokoyama T, Sato K, Sato T, Doi Y, Sugiura T (2010) Effects of various doses of aspirin on platelet activity and endothelial function. Heart Vessels. doi:10.1007/s00380-00010-00054-00388

  30. Hwang YS, Tsai WC, Lu YH, Lin CC, Chen YF (2004) Effect of atorvastatin on the expression of CD40 ligand and p-selectin on platelets in patients with hypercholesterolemia. Am J Cardiol 94:364–366

    Article  PubMed  CAS  Google Scholar 

  31. Oka H, Ikeda S, Koga S, Miyahara Y, Kohno S (2008) Atorvastatin induces associated reductions in platelet p-selectin, oxidized low-density lipoprotein, and interleukin-6 in patients with coronary artery diseases. Heart Vessels 23:249–256

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank H. Pirzer for critical reading of the manuscript and helpful suggestions.

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The authors declare that they have no conflict of interest.

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Correspondence to Thorsten Kälsch.

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R. Pirzer and E. Elmas contributed equally to this work.

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Pirzer, R., Elmas, E., Haghi, D. et al. Platelet and monocyte activity markers and mediators of inflammation in Takotsubo cardiomyopathy. Heart Vessels 27, 186–192 (2012). https://doi.org/10.1007/s00380-011-0132-6

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  • DOI: https://doi.org/10.1007/s00380-011-0132-6

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