Skip to main content

Advertisement

Log in

Phenotypic and Functional Alterations on Inflammatory Peripheral Blood Cells After Acute Myocardial Infarction

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

The frequency and function of T cells, monocytes, and dendritic cell subsets were investigated in 12 patients after acute myocardial infarction (AMI)—(T0), 1 month after the episode (T1), and in 12 healthy individuals (HG). The cell characterization and the functional studies were performed by flow cytometry and by RT-PCR, after cell sorting. The most important findings at T0 moment, when compared with T1 and HG, were: a decrease in the frequency of IL-2-producing T cells; a lower frequency of TNF-α- and IL-6-producing monocytes, myeloid dendritic cells, and CD14−/lowCD16+DCs; and a lower TNF-α mRNA expression, after sorting these cells. Moreover, the regulatory function of Treg cells, at T0 moment, was upregulated, based on the FoxP3, CTLA-4, and TGF-β mRNA expression increase. The majority of these phenotypic and functional alterations disappeared at T1. Our data demonstrate that AMI induces a significant change in the immune system homeostasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Alpert, J. S., Thygesen, K., Antman, E., & Bassand, J. P. (2000). Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. Journal of the American College of Cardiology, 36(3), 959–969.

    Article  PubMed  CAS  Google Scholar 

  2. Sun, Y. (2009). Myocardial repair/remodelling following infarction: roles of local factors. Cardiovascular Research, 81(3), 482–490. doi:10.1093/cvr/cvn333.

    Article  PubMed  CAS  Google Scholar 

  3. Frangogiannis, N. G., Smith, C. W., & Entman, M. L. (2002). The inflammatory response in myocardial infarction. Cardiovascular Research, 53(1), 31–47.

    Article  PubMed  CAS  Google Scholar 

  4. Deten, A., Volz, H. C., Briest, W., & Zimmer, H. G. (2002). Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovascular Research, 55(2), 329–340.

    Article  PubMed  CAS  Google Scholar 

  5. Irwin, M. W., Mak, S., Mann, D. L., Qu, R., Penninger, J. M., Yan, A., et al. (1999). Tissue expression and immunolocalization of tumor necrosis factor-alpha in postinfarction dysfunctional myocardium. Circulation, 99(11), 1492–1498.

    PubMed  CAS  Google Scholar 

  6. Akasaka, Y., Morimoto, N., Ishikawa, Y., Fujita, K., Ito, K., Kimura-Matsumoto, M., et al. (2006). Myocardial apoptosis associated with the expression of proinflammatory cytokines during the course of myocardial infarction. Modern Pathology, 19(4), 588–598. doi:10.1038/modpathol.3800568.

    Article  PubMed  CAS  Google Scholar 

  7. Frangogiannis, N. G. (2008). The immune system and cardiac repair. Pharmacological Research, 58(2), 88–111. doi:10.1016/j.phrs.2008.06.007.

    Article  PubMed  CAS  Google Scholar 

  8. Frangogiannis, N. G. (2006). The mechanistic basis of infarct healing. Antioxidants & Redox Signaling, 8(11–12), 1907–1939. doi:10.1089/ars.2006.8.1907.

    Article  CAS  Google Scholar 

  9. Nian, M., Lee, P., Khaper, N., & Liu, P. (2004). Inflammatory cytokines and postmyocardial infarction remodeling. Circulation Research, 94(12), 1543–1553. doi:10.1161/01.RES.0000130526.20854.

    Article  PubMed  CAS  Google Scholar 

  10. Biswas, S., Ghoshal, P. K., Mandal, S. C., & Mandal, N. (2010). Relation of anti- to pro-inflammatory cytokine ratios with acute myocardial infarction. The Korean Journal of Internal Medicine, 25(1), 44–50. doi:10.3904/kjim.2010.25.1.44.

    Article  PubMed  CAS  Google Scholar 

  11. Jiang, B., & Liao, R. (2010). The paradoxical role of inflammation in cardiac repair and regeneration. Journal of Cardiovascular Translational Research, 3(4), 410–416. doi:10.1007/s12265-010-9193-7.

    Article  PubMed  Google Scholar 

  12. Frantz, S., Bauersachs, J., & Ertl, G. (2009). Post-infarct remodelling: contribution of wound healing and inflammation. Cardiovascular Research, 81(3), 474–481. doi:10.1093/cvr/cvn292.

    Article  PubMed  CAS  Google Scholar 

  13. Almeida, J., Bueno, C., Alguero, M. C., Sanchez, M. L., de Santiago, M., Escribano, L., et al. (2001). Comparative analysis of the morphological, cytochemical, immunophenotypical, and functional characteristics of normal human peripheral blood lineage(−)/CD16(+)/HLA-DR(+)/CD14(−/lo) cells, CD14(+) monocytes, and CD16(−) dendritic cells. Clinical Immunology, 100(3), 325–338. doi:10.1006/clim.2001.5072.

    Article  PubMed  CAS  Google Scholar 

  14. Bueno, C., Almeida, J., Alguero, M. C., Sanchez, M. L., Vaquero, J. M., Laso, F. J., et al. (2001). Flow cytometric analysis of cytokine production by normal human peripheral blood dendritic cells and monocytes: comparative analysis of different stimuli, secretion-blocking agents and incubation periods. Cytometry, 46(1), 33–40. doi:10.1002/1097-0320(20010215).

    Article  PubMed  CAS  Google Scholar 

  15. MacDonald, K. P., Munster, D. J., Clark, G. J., Dzionek, A., Schmitz, J., & Hart, D. N. (2002). Characterization of human blood dendritic cell subsets. Blood, 100(13), 4512–4520. doi:10.1182/blood-2001-11-0097.

    Article  PubMed  CAS  Google Scholar 

  16. Crespo, I., Paiva, A., Couceiro, A., Pimentel, P., Orfao, A., & Regateiro, F. (2004). Immunophenotypic and functional characterization of cord blood dendritic cells. Stem Cells and Development, 13(1), 63–70. doi:10.1089/154732804773099263.

    Article  PubMed  CAS  Google Scholar 

  17. Henriques, A., Ines, L., Carvalheiro, T., Couto, M., Andrade, A., & Pedreiro, S. (2011). Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus. Rheumatology International. doi:10.1007/s00296-010-1709-6.

  18. Morgado, J. M., Pratas, R., Laranjeira, P., Henriques, A., Crespo, I., Regateiro, F., et al. (2008). The phenotypical and functional characteristics of cord blood monocytes and CD14(−/low)/CD16(+) dendritic cells can be relevant to the development of cellular immune responses after transplantation. Transplant Immunology, 19(1), 55–63. doi:10.1016/j.trim.2007.11.002.

    Article  PubMed  CAS  Google Scholar 

  19. Henriques, A., Ines, L., Couto, M., Pedreiro, S., Santos, C., Magalhaes, M., et al. (2010). Frequency and functional activity of Th17, Tc17 and other T-cell subsets in systemic lupus erythematosus. Cellular Immunology, 264(1), 97–103. doi:10.1016/j.cellimm.2010.05.004.

    Article  PubMed  CAS  Google Scholar 

  20. Paiva, A., Ferreira, T., Freitas, A., Couceiro, A., Coimbra, H., & Regateiro, F. J. (2000). Profile of cytokine production in human cord blood and peripheral blood from healthy donors before and after allogeneic activation: relevance in predicting graft-versus-host disease. Transplantation Proceedings, 32(8), 2626–2630.

    Article  PubMed  CAS  Google Scholar 

  21. Banham, A. H. (2006). Cell-surface IL-7 receptor expression facilitates the purification of FOXP3(+) regulatory T cells. Trends in Immunology, 27(12), 541–544. doi:10.1016/j.it.2006.10.002.

    Article  PubMed  CAS  Google Scholar 

  22. Caton, A. J., Cozzo, C., Larkin, J., 3rd, Lerman, M. A., Boesteanu, A., & Jordan, M. S. (2004). CD4(+) CD25(+) regulatory T cell selection. Annals of the New York Academy of Sciences, 1029, 101–114. doi:1029/1/101.

    Article  PubMed  CAS  Google Scholar 

  23. Corthay, A. (2009). How do regulatory T cells work? Scandinavian Journal of Immunology, 70(4), 326–336. doi:10.1111/j.1365-3083.2009.02308.x.

    Article  PubMed  CAS  Google Scholar 

  24. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3 (7):RESEARCH0034.

    Google Scholar 

  25. Ren, G., Dewald, O., & Frangogiannis, N. G. (2003). Inflammatory mechanisms in myocardial infarction. Current Drug Targets. Inflammation and Allergy, 2(3), 242–256.

    Article  PubMed  CAS  Google Scholar 

  26. Tousoulis, D., Charakida, M., & Stefanadis, C. (2008). Endothelial function and inflammation in coronary artery disease. Postgraduate Medical Journal, 84(993), 368–371. doi:10.1136/hrt.2005.066936.

    Article  PubMed  CAS  Google Scholar 

  27. Tarzami, S. T. (2011). Chemokines and inflammation in heart disease: adaptive or maladaptive? International Journal of Clinical Experimental Medicine, 4(1), 74–80.

    PubMed  Google Scholar 

  28. Parissis, J. T., Adamopoulos, S., Venetsanou, K., Kostakis, G., Rigas, A., Karas, S. M., et al. (2004). Plasma profiles of circulating granulocyte-macrophage colony-stimulating factor and soluble cellular adhesion molecules in acute myocardial infarction. Contribution to post-infarction left ventricular dysfunction. European Cytokine Network, 15(2), 139–144.

    PubMed  CAS  Google Scholar 

  29. Novo, G., Rizzo, M., La Carruba, S., Caruso, M., Amoroso, G. R., Balistreri, C. R., et al. (2011). The role of macrophage colony-stimulating factor in patients with acute myocardial infarction: a pilot study. Angiology. doi:10.1177/0003319711409742.

  30. Oren, H., Erbay, A. R., Balci, M., & Cehreli, S. (2007). Role of novel mediators of inflammation in left ventricular remodeling in patients with acute myocardial infarction: do they affect the outcome of patients? Angiology, 58(1), 45–54. doi:10.1177/0003319706297916.

    Article  PubMed  Google Scholar 

  31. Leone, A. M., Rutella, S., Bonanno, G., Contemi, A. M., de Ritis, D. G., Giannico, M. B., et al. (2006). Endogenous G-CSF and CD34+ cell mobilization after acute myocardial infarction. International Journal of Cardiology, 111(2), 202–208. doi:10.1016/j.ijcard.2005.06.043.

    Article  PubMed  Google Scholar 

  32. Nahrendorf, M., Pittet, M. J., & Swirski, F. K. (2010). Monocytes: protagonists of infarct inflammation and repair after myocardial infarction. Circulation, 121(22), 2437–2445. doi:10.1161/CIRCULATIONAHA.109.916346.

    Article  PubMed  Google Scholar 

  33. Nahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J. L., et al. (2007). The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. The Journal of Experimental Medicine, 204(12), 3037–3047. doi:10.1084/jem.20070885.

    Article  PubMed  CAS  Google Scholar 

  34. Kofler, S., Sisic, Z., Shvets, N., Lohse, P., & Weis, M. (2011). Expression of circulatory dendritic cells and regulatory T-cells in patients with different subsets of coronary artery disease. Journal of Cardiovascular Pharmacology, 57(5), 542–549. doi:10.1097/FJC.0b013e3182124c53.

    Article  PubMed  CAS  Google Scholar 

  35. Tu, X. W., Li, Z. L., Liu, Y. F., & Wei, X. L. (2009). Classification and functional study of peripheral blood dendritic cells in patients with coronary artery disease with different atherosclerotic plaques. Nan Fang Yi Ke Da Xue Xue Bao, 29(6), 1195–1198.

    PubMed  CAS  Google Scholar 

  36. Van Brussel, I., Van Vre, E. A., De Meyer, G. R., Vrints, C. J., Bosmans, J. M., & Bult, H. (2011). Decreased numbers of peripheral blood dendritic cells in patients with coronary artery disease are associated with diminished plasma Flt3 ligand levels and impaired plasmacytoid dendritic cell function. Clinical Science (London, England), 120(9), 415–426. doi:10.1042/CS20100440.

    Article  Google Scholar 

  37. Van Vre, E. A., Hoymans, V. Y., Bult, H., Lenjou, M., Van Bockstaele, D. R., Vrints, C. J., et al. (2006). Decreased number of circulating plasmacytoid dendritic cells in patients with atherosclerotic coronary artery disease. Coronary Artery Disease, 17(3), 243–248.

    Article  PubMed  Google Scholar 

  38. Dinman, J. D. (2005). 5S rRNA: structure and function from head to toe. International Journal of Biomedical Sciences, 1(1), 2–7.

    Google Scholar 

  39. Tsujioka, H., Imanishi, T., Ikejima, H., Kuroi, A., Takarada, S., Tanimoto, T., et al. (2009). Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. Journal of the American College of Cardiology, 54(2), 130–138. doi:10.1016/j.jacc.2009.04.021.

    Article  PubMed  Google Scholar 

  40. Nah, D. Y., & Rhee, M. Y. (2009). The inflammatory response and cardiac repair after myocardial infarction. Korean Circulation Journal, 39(10), 393–398. doi:10.4070/kcj.2009.39.10.393.

    Article  PubMed  CAS  Google Scholar 

  41. Yip, H. K., Youssef, A. A., Chang, L. T., Yang, C. H., Sheu, J. J., Chua, S., et al. (2007). Association of interleukin-10 level with increased 30-day mortality in patients with ST-segment elevation acute myocardial infarction undergoing primary coronary intervention. Circulation Journal, 71(7), 1086–1091.

    Article  PubMed  CAS  Google Scholar 

  42. Karpinski, L., Plaksej, R., Derzhko, R., Orda, A., & Witkowska, M. (2009). Serum levels of interleukin-6, interleukin-10 and C-reactive protein in patients with myocardial infarction treated with primary angioplasty during a 6-month follow-up. Polskie Archiwum Medycyny Wewnętrznej, 119(3), 115–121.

    PubMed  CAS  Google Scholar 

  43. Kempf, T., Eden, M., Strelau, J., Naguib, M., Willenbockel, C., Tongers, J., et al. (2006). The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circulation Research, 98(3), 351–360. doi:10.1161/01.RES.0000202805.73038.48.

    Article  PubMed  CAS  Google Scholar 

  44. Bujak, M., & Frangogiannis, N. G. (2007). The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovascular Research, 74(2), 184–195. doi:10.1016/j.cardiores.2006.10.002.

    Article  PubMed  CAS  Google Scholar 

  45. Haeusler, K. G., Schmidt, W. U., Foehring, F., Meisel, C., Guenther, C., Brunecker, P., et al. (2010). Immune responses after acute ischemic stroke or myocardial infarction. International Journal of Cardiology. doi:10.1016/j.ijcard.2010.10.053.

  46. Hansson, G. K., & Libby, P. (2006). The immune response in atherosclerosis: a double-edged sword. Nature Reviews Immunology, 6(7), 508–519. doi:10.1038/nri1882.

    Article  PubMed  CAS  Google Scholar 

  47. Cheng, X., Liao, Y. H., Ge, H., Li, B., Zhang, J., Yuan, J., et al. (2005). TH1/TH2 functional imbalance after acute myocardial infarction: coronary arterial inflammation or myocardial inflammation. Journal of Clinical Immunology, 25(3), 246–253. doi:10.1007/s10875-005-4088-0.

    Article  PubMed  CAS  Google Scholar 

  48. Steppich, B. A., Moog, P., Matissek, C., Wisniowski, N., Kuhle, J., Joghetaei, N., et al. (2007). Cytokine profiles and T cell function in acute coronary syndromes. Atherosclerosis, 190(2), 443–451. doi:10.1016/j.atherosclerosis.2006.02.034.

    Article  PubMed  CAS  Google Scholar 

  49. Bodi, V., Sanchis, J., Nunez, J., Mainar, L., Minana, G., Benet, I., et al. (2008). Uncontrolled immune response in acute myocardial infarction: unraveling the thread. American Heart Journal, 156(6), 1065–1073. doi:10.1016/j.ahj.2008.07.008.

    Article  PubMed  CAS  Google Scholar 

  50. Sardella, G., De Luca, L., Francavilla, V., Accapezzato, D., Mancone, M., Sirinian, M. I., et al. (2007). Frequency of naturally-occurring regulatory T cells is reduced in patients with ST-segment elevation myocardial infarction. Thrombosis Research, 120(4), 631–634. doi:10.1016/j.thromres.2006.12.005.

    Article  PubMed  CAS  Google Scholar 

  51. Han, S. F., Liu, P., Zhang, W., Bu, L., Shen, M., Li, H., et al. (2007). The opposite-direction modulation of CD4+ CD25+ Tregs and T helper 1 cells in acute coronary syndromes. Clinical Immunology, 124(1), 90–97. doi:10.1016/j.clim.2007.03.546.

    Article  PubMed  CAS  Google Scholar 

  52. Ammirati, E., Cianflone, D., Banfi, M., Vecchio, V., Palini, A., De Metrio, M., et al. (2010). Circulating CD4+ CD25hiCD127lo regulatory T-cell levels do not reflect the extent or severity of carotid and coronary atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(9), 1832–1841. doi:10.1161/ATVBAHA.110.206813.

    Article  PubMed  CAS  Google Scholar 

  53. Mor, A., Luboshits, G., Planer, D., Keren, G., & George, J. (2006). Altered status of CD4(+)CD25(+) regulatory T cells in patients with acute coronary syndromes. European Heart Journal, 27(21), 2530–2537. doi:10.1093/eurheartj/ehl222.

    Article  PubMed  CAS  Google Scholar 

  54. de Boer, O. J., van der Meer, J. J., Teeling, P., van der Loos, C. M., & van der Wal, A. C. (2007). Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions. PloS One, 2(8), e779. doi:10.1371/journal.pone.0000779.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Letícia Nunes, Diana Ferreira, Filipe Vilela, Liliana Oliveira, and Sofia Pereira from the Superior School of Health Technology of Coimbra for their contribution on sample processing.

Ethical Standards

The study protocol was approved by the local ethics committee. All participants gave and signed informed consent, and the principles of the Helsinki Declaration were respected.

Conflict of Interest

None are disclosed.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Artur Paiva.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carvalheiro, T., Velada, I., Valado, A. et al. Phenotypic and Functional Alterations on Inflammatory Peripheral Blood Cells After Acute Myocardial Infarction. J. of Cardiovasc. Trans. Res. 5, 309–320 (2012). https://doi.org/10.1007/s12265-012-9365-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-012-9365-8

Keywords

Navigation