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The Elevated Serum S100A8/A9 During Acute Myocardial Infarction Is Not of Cardiac Myocyte Origin

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Abstract

Overproduction of circulating S100A8/A9 occurs in patients following acute myocardial infarction (AMI). It remains unclear whether ischemia insult per se induces S100A8 and S100A9 expression in cardiac myocytes or even whether the cardiac myocytes participate as a source of these proteins. In this study, western blot analysis and quantitative real-time reverse transcription polymerase chain reaction were used to test samples obtained from isolated spontaneously hypertensive rat hearts and Wistar-Kyoto rat hearts subjected to global normothermic ischemia and from neonatal Wistar rat cardiac myocytes undergoing hypoxia. Ischemia did not increase the expression of S100A8 and S100A9 proteins and mRNA in the myocardium either from the spontaneously hypertensive rat hearts or the Wistar-Kyoto rat hearts. In addition, the levels of S100A8 and S100A9 proteins were unchanged in the neonatal rat cardiac myocytes undergoing hypoxia. However, both ischemia and hypoxia activated NF-kappaB in ischemic myocardium and in hypoxic cardiac cells in a time-dependent manner. The results suggest that the increased serum S100A8/A9 concentrations following AMI were not of cardiac myocyte origin.

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Abbreviations

ACS:

Acute coronary syndrome

AMI:

Acute myocardial infarction

SHR:

Spontaneously hypertensive rats

WKY:

Wistar-Kyoto rats

PBS:

Phosphate-buffered saline

LVEDP:

Left ventricular end-diastolic pressure

LVDP:

Left ventricular developed pressure

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

RT-qPCR:

Quantitative real-time reverse transcription polymerase chain reaction

LPS:

Lipopolysaccharide

PMN:

Polymorphonuclear leukocytes

IL-1β:

Interleukin-1 beta

TNF-α:

Tumor necrosis factor alpha

IL-1α:

Interleukin-1 alpha

TGF-β:

Transforming growth factor beta

RAGE:

Receptor for advanced glycosylation end products

References

  1. Teigelkamp, S., R.S. Bhardwaj, J. Roth, G. Meinardus-Hager, M. Karas, and C. Sorg. 1991. Calcium-dependent complex assembly of the myeloic differentiation proteins MRP-8 and MRP-14. Journal of Biological Chemistry 266: 13462–13467.

    PubMed  CAS  Google Scholar 

  2. Foell, D., M. Frosch, C. Sorg, and J. Roth. 2004. Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation. Clinica Chimica Acta 344: 37–51.

    Article  CAS  Google Scholar 

  3. Striz, I., and I. Trebichavsky. 2004. Calprotectin: a pleiotropic molecule in acute and chronic inflammation. Physiological Research 53: 245–253.

    PubMed  CAS  Google Scholar 

  4. Vogl, T., K. Tenbrock, S. Ludwig, N. Leukert, C. Ehrhardt, M.A. van Zoelen, et al. 2007. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nature Medicine 13: 1042–1049.

    Article  PubMed  CAS  Google Scholar 

  5. Ehrchen, J.M., C. Sunderkötter, D. Foell, T. Vogl, and J. Roth. 2009. The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. Journal of Leukocyte Biology 86: 557–566.

    Article  PubMed  CAS  Google Scholar 

  6. Morrow, D.A., Y. Wang, K. Croce, M. Sakuma, M.S. Sabatine, H. Gao, et al. 2008. Myeloid-related protein-8/14 and the risk of cardiovascular death or myocardial infarction after an acute coronary syndrome in the PROVE IT-TIMI 22 Trial. American Heart Journal 155: 49–55.

    Article  PubMed  CAS  Google Scholar 

  7. Healy, A.M., M.D. Pickard, A.D. Pradhan, Y. Wang, Z. Chen, K. Croce, et al. 2006. Platelet expression profiling and clinical validation of myeloid-related protein-14 as a novel determinant of cardiovascular events. Circulation 113: 2278–2284.

    Article  PubMed  CAS  Google Scholar 

  8. Altwegg, L.A., M. Neidhart, M. Hersberger, S. Müller, F.R. Eberli, R. Corti, et al. 2007. Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes. European Heart Journal 28: 941–948.

    Article  PubMed  CAS  Google Scholar 

  9. Miyamoto, S., M. Ueda, M. Ikemoto, T. Naruko, A. Itoh, S. Tamaki, et al. 2008. Increased serum levels and expression of S100A8/A9 complex in infiltrated neutrophils in atherosclerotic plaque of unstable angina. Heart 94: 1002–1007.

    Article  PubMed  CAS  Google Scholar 

  10. Katashima, T., T. Naruko, F. Terasaki, M. Fujita, K. Otsuka, S. Murakami, et al. 2010. Enhanced expression of the S100A8/A9 complex in acute myocardial infarction patients. Circulation Journal 74: 741–748.

    Article  PubMed  CAS  Google Scholar 

  11. McCormick, M.M., F. Rahimi, Y.V. Bobryshev, K. Gaus, H. Zreiqat, H. Cai, et al. 2005. S100A8 and S100A9 in human arterial wall: Implications for atherogenesis. Journal of Biological Chemistry 280: 41521–41529.

    Article  PubMed  CAS  Google Scholar 

  12. Mues, B., B. Brisse, G. Zwadlo, H. Themann, F. Bender, and C. Sorg. 1990. Phenotyping of macrophages with monoclonal antibodies in endomyocardial biopsies as a new approach to diagnosis of myocarditis. European Heart Journal 11: 619–627.

    PubMed  CAS  Google Scholar 

  13. Boyd, J.H., B. Kan, H. Roberts, Y. Wang, and K.R. Walley. 2008. S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products. Circulation Research 102: 1239–1246.

    Article  PubMed  CAS  Google Scholar 

  14. Bouma, G., W.K. Lam-Tse, A.F. Wierenga-Wolf, H.A. Drexhage, and M.A. Versnel. 2004. Increased serum levels of MRP-8/14 in type 1 diabetes induce an increased expression of CD11b and an enhanced adhesion of circulating monocytes to fibronectin. Diabetes 53: 1979–1986.

    Article  PubMed  CAS  Google Scholar 

  15. Semb, A.G., T.O. Gabrielsen, T.S. Halstensen, M.K. Fagerhol, P. Brandtzaeg, and J. Vaage. 1991. Cardiac surgery and distribution of the leukocyte Ll protein-calprotectin. European Journal of Cardio-Thoracic Surgery 5: 363–367.

    Article  PubMed  CAS  Google Scholar 

  16. Neumann, F.J., I. Ott, M. Gawaz, G. Richardt, H. Holzapfel, M. Jochum, et al. 1995. Cardiac release of cytokines and inflammatory responses in acute myocardial infarction. Circulation 92: 748–755.

    PubMed  CAS  Google Scholar 

  17. Edgeworth, J., M. Gorman, R. Bennett, P. Freemont, and N. Hogg. 1991. Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. Journal of Biological Chemistry 266: 7706–7713.

    PubMed  CAS  Google Scholar 

  18. Inaba, H., K. Hokamura, K. Nakano, R. Nomura, K. Katayama, A. Nakajima, et al. 2009. Upregulation of S100 calcium-binding protein A9 is required for induction of smooth muscle cell proliferation by a periodontal pathogen H. FEBS Letters 583: 128–134.

    Article  PubMed  CAS  Google Scholar 

  19. Rahimi, F., K. Hsu, Y. Endoh, and C.L. Geczy. 2005. FGF-2, IL-1b and TGF-b regulate fibroblast expression of S100A8. FEBS Journal 272: 2811–2827.

    Article  PubMed  CAS  Google Scholar 

  20. Nishikimi, T., H. Yamagishi, K. Takeuchi, and T. Takeda. 1995. An angiotensin II receptor antagonist attenuates left ventricular dilatation after myocardial infarction in the hypertensive rat. Cardiovascular Research 29: 856–861.

    PubMed  CAS  Google Scholar 

  21. Kodavanti, U.P., M.C. Schladweiler, A.D. Ledbetter, W.P. Watkinson, M.J. Campen, D.W. Winsett, et al. 2000. The spontaneously hypertensive rat as a model of human cardiovascular disease: evidence of exacerbated cardiopulmonary injury and oxidative stress from inhaled emission particulate matter. Toxicology and Applied Pharmacology 164: 250–263.

    Article  PubMed  CAS  Google Scholar 

  22. Kubota, Y., K. Umegaki, S. Kagota, N. Tanaka, K. Nakamura, M. Kunitomo, et al. 2006. Evaluation of blood pressure measured by tail-cuff methods (without heating) in spontaneously hypertensive rats. Biological and Pharmaceutical Bulletin 29: 1756–1758.

    Article  PubMed  CAS  Google Scholar 

  23. Yang, Y., S.J. Hu, L. Li, and G.P. Chen. 2009. Cardioprotection by polysaccharide sulfate against ischemia/reperfusion injury in isolated rat hearts. Acta Pharmacologica Sinica 30: 54–60.

    Article  PubMed  Google Scholar 

  24. Ye, Y., S.J. Hu, and L. Li. 2009. Inhibition of farnesylpyrophosphate synthase prevents angiotensin II-induced hypertrophic responses in rat neonatal cardiomyocytes: involvement of the RhoA/Rho kinase pathway. FEBS Letters 583: 2997–3003.

    Article  PubMed  CAS  Google Scholar 

  25. Kacimi, R., C.S. Long, and J.S. Karliner. 1997. Chronic hypoxia modulates IL-1binduced nitric oxide synthase signaling in neonatal ventricular myocytes. Circulation 96: 1937–1943.

    PubMed  CAS  Google Scholar 

  26. Hermani, A., B. De Servi, S. Medunjanin, P.A. Tessier, and D. Mayer. 2006. S100A8 and S100A9 activate MAP kinase and NF-kappaB signaling pathways and trigger translocation of RAGE in human prostate cancer cells. Experimental Cell Research 312: 184–197.

    Article  PubMed  CAS  Google Scholar 

  27. Simkhovich, B.Z., P. Marjoram, C. Poizat, L. Kedes, and R.A. Kloner. 2003. Brief episode of ischemia activates protective genetic program in rat heart: A gene chip study. Cardiovascular Research 59: 450–459.

    Article  PubMed  CAS  Google Scholar 

  28. Ionita, M.G., A. Vink, I.E. Dijke, J.D. Laman, W. Peeters, P.H. van der Kraak, et al. 2009. High levels of myeloid-related protein 14 in human atherosclerotic plaques correlate with the characteristics of rupture-prone lesions. Arteriosclerosis, Thrombosis, and Vascular Biology 29: 1220–1227.

    Article  PubMed  CAS  Google Scholar 

  29. Djurdjevic, P.M., N.N. Arsenijevic, D.D. Baskic, A.L. Djukic, S. Popovic, and G. Samardzic. 2001. Systemic response of peripheral blood leukocytes and their phagocytic activity during acute myocardial infarction. Experimental and Clinical Cardiology 6: 159–166.

    PubMed  CAS  Google Scholar 

  30. Goyette, J., and C.L. Geczy. 2011. Inflammation-associated S100 proteins: new mechanisms that regulate function. Amino Acids (in press).

  31. Ross, K.F., and M.C. Herzberg. 2001. Calprotectin expression by gingival epithelial cells. Infection and Immunity 69: 3248–3254.

    Article  PubMed  CAS  Google Scholar 

  32. Bando, M., Y. Hiroshima, M. Kataoka, Y. Shinohara, M.C. Herzberg, K.F. Ross, et al. 2007. Interleukin-1alpha regulates antimicrobial peptide expression in human keratinocytes. Immunology and Cell Biology 85: 532–537.

    Article  PubMed  CAS  Google Scholar 

  33. Rammes, A., J. Roth, M. Goebeler, M. Klempt, M. Hartmann, and C. Sorg. 1997. Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway. Journal of Biological Chemistry 272: 9496–9502.

    Article  PubMed  CAS  Google Scholar 

  34. Kido, J., N. Hayashi, M. Kataoka, and T. Nagata. 2005. Calprotectin expression in human monocytes: Induction by porphyromonas gingivalis lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-1beta. Journal of Periodontology 76: 437–442.

    Article  PubMed  Google Scholar 

  35. Frosch, M., A. Strey, T. Vogl, N.M. Wulffraat, W. Kuis, C. Sunderkötter, et al. 2000. Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis. Arthritis and Rheumatism 43: 628–637.

    Article  PubMed  CAS  Google Scholar 

  36. Hsu, K., C. Champaiboon, B.D. Guenther, B.S. Sorenson, A. Khammanivong, K.F. Ross, et al. 2009. Anti-infective protective properties of S100 calgranulins. Antiinflamm Antiallergy Agents Med Chem 8: 290–305.

    PubMed  CAS  Google Scholar 

  37. Alexander, R.W. 1994. Inflammation and coronary artery disease. The New England Journal of Medicine 331: 468–469.

    Article  PubMed  CAS  Google Scholar 

  38. Nian, M., P. Lee, N. Khaper, and P. Liu. 2004. Inflammatory cytokines and post-myocardial infarction remodeling. Circulation Research 94: 1543–1553.

    Article  PubMed  CAS  Google Scholar 

  39. Cain, B.S., D.R. Meldrum, C.A. Dinarello, X. Meng, K.S. Joo, A. Banerjeeet, et al. 1999. Tumor necrosis factor-alpha and interleukin-1beta synergistically depress human myocardial function. Critical Care Medicine 27: 1309–1318.

    Article  PubMed  CAS  Google Scholar 

  40. Nacken, W., J. Roth, C. Sorg, and C. Kerkhoff. 2003. S100A9/S100A8: Myeloid representatives of the S100 protein family as prominent players in innate immunity. Micros Res Tech 60: 569–580.

    Article  CAS  Google Scholar 

  41. Carroccio, A., P. Rocco, P.G. Rabitti, L. Di Prima, G.B. Forte, and A.B. Cefalu. 2006. Plasma calprotectin levels in patients suffering from acute pancreatitis. Digestive Diseases and Sciences 51: 1749–1753.

    Article  PubMed  CAS  Google Scholar 

  42. Homann, C., E. Christensen, P. Schlichting, E.K. Philipsen, N.A. Graudal, and P. Garred. 2003. Ascites fluid and plasma calprotectin concentrations in liver disease. Scandinavian Journal of Gastroenterology 38: 415–420.

    Article  PubMed  CAS  Google Scholar 

  43. Shames, B.D., H.H. Barton, L.L. Reznikov, C.B. Cairns, A. Banerjee, A.H. Harken, et al. 2002. Ischemia alone is sufficient to induce TNF-alpha mRNA and peptide in the myocardium. Shock 17: 114–119.

    Article  PubMed  Google Scholar 

  44. Kacimi, R., J.S. Karliner, F. Koudssi, and C.S. Long. 1998. Expression and regulation of adhesion molecules in cardiac cells: response to acute hypoxia. Circulation Research 82: 576–586.

    PubMed  CAS  Google Scholar 

  45. Gupta, S., D. Young, and S. Sen. 2005. Inhibition of NF-kappaB induces regression of cardiac hypertrophy, independent of blood pressure control, in spontaneously hypertensive rats. American Journal of Physiology-Heart and Circulatory Physiology 289: H20–H29.

    Article  PubMed  CAS  Google Scholar 

  46. Gerhardt, W., and L. Ljungdahl. 1998. Troponin T: A sensitive and specific diagnostic and prognostic marker of myocardial damage. Clinica Chimica Acta 272: 47–57.

    Article  CAS  Google Scholar 

  47. Sutherland, F.J., and D.J. Hearse. 2000. The isolated blood and perfusion fluid perfused heart. Pharmacological Research 41: 613–627.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Sciences Foundation of China (project numbers 30470715, 30870939) and the Research Fund for the Doctoral Program of Higher Education of China (no. 20040335118).

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The authors have no conflicting financial interests.

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Correspondence to Shen-Jiang Hu.

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Chang-Qing Du and Lin Yang contributed equally to this work.

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Du, CQ., Yang, L., Han, J. et al. The Elevated Serum S100A8/A9 During Acute Myocardial Infarction Is Not of Cardiac Myocyte Origin. Inflammation 35, 787–796 (2012). https://doi.org/10.1007/s10753-011-9375-8

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  • DOI: https://doi.org/10.1007/s10753-011-9375-8

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