Skip to main content

Advertisement

SpringerLink
Log in

Association of circulating levels of RANTES and −403G/A promoter polymorphism to acute heart failure after STEMI and to cardiogenic shock

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Chemokines, including RANTES, play a crucial role in the processes of inflammation during cardiovascular disorders, including myocardial infarction, disease progression and complications. This study aimed to evaluate the role of RANTES −403G/A polymorphism and levels in circulation in processes of development and progression of myocardial infarction and cardiogenic shock. A total of 609 patients with ST-segment elevation myocardial infarction, 43 patients with cardiogenic shock and 130 control subjects were enrolled in the study. RANTES −403G/A promoter polymorphism and baseline serum RANTES levels were analyzed. In the present study, we associated RANTES −403G/A promoter polymorphism with acute heart failure in patients with myocardial infarction (p = 0.006) and ejection fraction 3 months after MI onset (p = 0.02). Further, a difference in circulating RANTES levels among controls and STEMI subjects, and a relation of serum levels with acute heart failure was observed (p = 0.03, p = 0.003, respectively). We found a significant difference when comparing cardiogenic shock patients and controls (p < 0.001), with the most significant difference between cardiogenic shock and AHF subgroup of STEMI patients (p < 0.001). We observed a decreasing tendency of serum RANTES levels with the severity of myocardial infarction and progression, with the lowest levels in patients with cardiogenic shock (cutoff level ≥80.4 ng/ml). Our results suggest the role of RANTES as a potential biomarker of cardiogenic shock and acute heart failure in the hospital phase after myocardial infarction.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Amoli MM, Miranda-Filloy JA, Vazquez-Rodriguez TR, Ollier WE, Gonzalez-Gay MA. Regulated upon activation normal T-cell expressed and secreted (RANTES) and epithelial cell-derived neutrophil-activating peptide (ENA-78) gene polymorphisms in patients with biopsy-proven erythema nodosum. Clin Exp Rheumatol. 2009;27:142–3.

    Google Scholar 

  2. Appay V, Rowland-Jones SL. RANTES: a versatile and controversial chemokine. Trends Immunol. 2001;22:83–7.

    Article  CAS  PubMed  Google Scholar 

  3. Aukrust P, Ueland T, Muller F, Andreassen AK, Nordoy I, Aas H, Kjekshus J, Simonsen S, Froland SS, Gullestad L. Elevated circulating levels of C–C chemokines in patients with congestive heart failure. Circulation. 1998;97:1136–43.

    Article  CAS  PubMed  Google Scholar 

  4. Aukrust P, Yndestad A, Smith C, Ueland T, Gullestad L, Damas JK. Chemokines in cardiovascular risk prediction. Thromb Haemost. 2007;97:748–54.

    CAS  PubMed  Google Scholar 

  5. Cavusoglu E, Eng C, Chopra V, Clark LT, Pinsky DJ, Marmur JD. Low plasma RANTES levels are an independent predictor of cardiac mortality in patients referred for coronary angiography. Arterioscler Thromb Vasc Biol. 2007;27:929–35.

    Article  CAS  PubMed  Google Scholar 

  6. Ciccone MM, Cortese F, Gesualdo M, Riccardi R, Di Nunzio D, Moncelli M, Iacoviello M, Scicchitano P. A novel cardiac bio-marker: ST2: a review. Molecules. 2013;18(12):15314–28.

    Article  CAS  PubMed  Google Scholar 

  7. Ellis M, Al-Ramadi B, Hedstrom U, Frampton C, Alizadeh H, Kristensen J. Significance of the CC chemokine RANTES in patients with haematological malignancy: results from a prospective observational study. Br J Haematol. 2005;128:482–9.

  8. ESC Guidelines: Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI), Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, Garg S, Huber K, James S, Knuuti J, Lopez-Sendon J, Marco J, Menicanti L, Ostojic M, Piepoli MF, Pirlet C, Pomar JL, Reifart N, Ribichini FL, Schalij MJ, Sergeant P, Serruys PW, Silber S, Sousa Uva M, Taggart D. Guidelines on myocardial revascularization. Eur Heart J. 2010;31(20):2501–55.

  9. Fryer AA, Spiteri MA, Bianco A, Hepple M, Jones PW, Strange RC, Makki R, Tavernier G, Smilie FI, Custovic A, Woodcock AA, Ollier WE, Hajeer AH. The −403G>A promoter polymorphism in the RANTES gene is associated with atopy and asthma. Genes Immun. 2000;1:509–14.

    Article  CAS  PubMed  Google Scholar 

  10. Gear AR, Camerini D. Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation. 2003;10:335–50.

    Article  CAS  PubMed  Google Scholar 

  11. Hajeer AH, Al Sharif F, Ollier WE. A polymorphism at position −403 in the human RANTES promoter. Eur J Immunogenet. 1999;26:375–6.

  12. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–95.

    Article  CAS  PubMed  Google Scholar 

  13. Hoogerwerf J, Tanck M, van Zoelen M, Wittebole X, Laterre PF, van der Poll T. Soluble ST2 plasma concentrations predict mortality in severe sepsis. Intensive Care Med. 2010;36:630–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jang Y, Chae JS, Hyun YJ, Koh SJ, Kim JY, Ko MJ, Rim SJ, Shin HJ, Ordovas JM, Lee JH. The RANTES −403G>A promoter polymorphism in Korean men: association with serum RANTES concentration and coronary artery disease. Clin Sci (Lond). 2007;113:349–56.

    Article  CAS  Google Scholar 

  15. Kala P, Kanovsky J, Rokyta R, Smid M, Pospisil J, Knot J, Rohac F, Poloczek M, Ondrus T, Holicka M, Spinar J, Jarkovsky J, Dusek L. Age-related treatment strategy and long-term outcome in acute myocardial infarction patients in the PCI era. BMC Cardiovasc Disord. 2012;12:31.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kobusiak-Prokopowicz M, Orzeszko J, Mazur G, Mysiak A, Orda A, Poreba R, Mazurek W. Chemokines and left ventricular function in patients with acute myocardial infarction. Eur J Intern Med. 2007;18:288–94.

    Article  CAS  PubMed  Google Scholar 

  17. Krohn R, Raffetseder U, Bot I, Zernecke A, Shagdarsuren E, Liehn EA, van Santbrink PJ, Nelson PJ, Biessen EA, Mertens PR, Weber C. Y-box binding protein-1 controls CC chemokine ligand-5 (CCL5) expression in smooth muscle cells and contributes to neointima formation in atherosclerosis-prone mice. Circulation. 2007;116:1812–20.

    Article  CAS  PubMed  Google Scholar 

  18. Liu J, Jia YJ, Li XL, Xu RX, Zhu CG, Guo YL, Wu NQ, Li JJ. RANTES gene G-403A polymorphism and coronary artery disease: a meta analysis of observational studies. PLoS ONE. 2012;7:47211.

    Article  Google Scholar 

  19. Matsumori A, Furukawa Y, Hashimoto T, Yoshida A, Ono K, Shioi T, Okada M, Iwasaki A, Nishio R, Matsushima K, Sasayama S. Plasma levels of the monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 are elevated in patients with acute myocardial infarction. J Mol Cell Cardiol. 1997;29:419–23.

    Article  CAS  PubMed  Google Scholar 

  20. Mause SF, von Hundelshausen P, Zernecke A, Koenen RR, Weber C. Platelet microparticles: a transcellular delivery system for RANTES promoting monocyte recruitment on endothelium. Arterioscler Thromb Vasc Biol. 2005;25:1512–8.

    Article  CAS  PubMed  Google Scholar 

  21. McDermott DH, Beecroft MJ, Kleeberger CA, Al-Sharif FM, Ollier WE, Zimmerman PA, Boatin BA, Leitman SF, Detels R, Hajeer AH, Murphy PM. Chemokine RANTES promoter polymorphism affects risk of both HIV infection and disease progression in the Multicenter AIDS Cohort Study. Aids. 2000;14:2671–8.

    Article  CAS  PubMed  Google Scholar 

  22. Nakajima K, Tanaka Y, Nomiyama T, Ogihara T, Ikeda F, Kanno R, Iwashita N, Sakai K, Watada H, Onuma T, Kawamori R. RANTES promoter genotype is associated with diabetic nephropathy in type 2 diabetic subjects. Diabetes Care. 2003;26:892–8.

    Article  CAS  PubMed  Google Scholar 

  23. Nickel RG, Casolaro V, Wahn U, Beyer K, Barnes KC, Plunkett BS, Freidhoff LR, Sengler C, Plitt JR, Schleimer RP, Caraballo L, Naidu RP, Levett PN, Beaty TH, Huang SK. Atopic dermatitis is associated with a functional mutation in the promoter of the C–C chemokine RANTES. J Immunol. 2000;164:1612–6.

    Article  CAS  PubMed  Google Scholar 

  24. Nystrom PO. The systemic inflammatory response syndrome: definitions and aetiology. J Antimicrob Chemother. 1998;41:1–7.

    Article  CAS  PubMed  Google Scholar 

  25. Packard RR, Libby P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem. 2008;54:24–38.

    Article  CAS  PubMed  Google Scholar 

  26. Parenica J, Malaska J, Jarkovsky J, Lipkova J, Dastych M, Helanova K, Litzman J, Tomandl J, Littnerova S, Sevcikova J, Gal R, Sevcik P, Spinar J. Pavkova Goldbergova M. Exp Clin Cardiol. 2012;17(4):205–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Parissis JT, Adamopoulos S, Venetsanou KF, Mentzikof DG, Karas SM, Kremastinos DT. Serum profiles of C–C chemokines in acute myocardial infarction: possible implication in postinfarction left ventricular remodeling. J Interferon Cytokine Res. 2002;22:223–9.

    Article  CAS  PubMed  Google Scholar 

  28. Pattison JM, Nelson PJ, Huie P, Sibley RK, Krensky AM. RANTES chemokine expression in transplant-associated accelerated atherosclerosis. J Heart Lung Transplant. 1996;15:1194–9.

    CAS  PubMed  Google Scholar 

  29. Pavkova Goldbergova M, Lipkova J, Pavek N, Gatterova J, Vasku A, Soucek M, Nemec P. RANTES, MCP-1 chemokines and factors describing rheumatoid arthritis. Mol Immunol. 2012;52:273–8.

    Article  CAS  PubMed  Google Scholar 

  30. Qin X, He Z, Zhao D, Li L, Yuan L. The RANTES gene promoter polymorphisms are associated with the risk of atherothrombotic cerebral infarction in Northern Han Chinese. Clin Chim Acta. 2011;412:1112–5.

    Article  CAS  PubMed  Google Scholar 

  31. Rothenbacher D, Muller-Scholze S, Herder C, Koenig W, Kolb H. Differential expression of chemokines, risk of stable coronary heart disease, and correlation with established cardiovascular risk markers. Arterioscler Thromb Vasc Biol. 2006;26:194–9.

    Article  CAS  PubMed  Google Scholar 

  32. Schal TJ. Biology of the RANTES/SIS cytokine family. Cytokine. 1991;3:165–83.

    Article  Google Scholar 

  33. Schober A, Manka D, von Hundelshausen P, Huo Y, Hanrath P, Sarembock IJ, Ley K, Weber C. Deposition of platelet RANTES triggering monocyte recruitment requires P-selectin and is involved in neointima formation after arterial injury. Circulation. 2002;106:1523–9.

    Article  CAS  PubMed  Google Scholar 

  34. Shimpo M, Morrow DA, Weinberg EO, Sabatine MS, Murphy SA, Antman EM, Lee RT. Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction. Circulation. 2004;109:2186–90.

    Article  CAS  PubMed  Google Scholar 

  35. Simeoni E, Winkelmann BR, Hoffmann MM, Fleury S, Ruiz J, Kappenberger L, Marz W, Vassalli G. Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis. Eur Heart J. 2004;25:1438–46.

    Article  CAS  PubMed  Google Scholar 

  36. Song A, Nikolcheva T, Krensky AM. Transcriptional regulation of RANTES expression in T lymphocytes. Immunol Rev. 2000;177:236–45.

    Article  CAS  PubMed  Google Scholar 

  37. Szalai C, Duba J, Prohaszka Z, Kalina A, Szabo T, Nagy B, Horvath L, Csaszar A. Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1-2518 G/G genotype in CAD patients. Atherosclerosis. 2001;158:233–9.

    Article  CAS  PubMed  Google Scholar 

  38. Tavakkoly-Bazzaz J, Amiri P, Tajmir-Riahi M, Javidi D, Khojasteh-Fard M, Taheri Z, Tabrizi A, Keramatipour M, Amoli MM. RANTES gene mRNA expression and its −403G/A promoter polymorphism in coronary artery disease. Gene. 2011;487:103–6.

    Article  CAS  PubMed  Google Scholar 

  39. Tereshchenko IP, Petrkova J, Voevoda MI, Taborsky M, Navratilova Z, Romaschenko AG, Maksimov VN, Mrazek F, Petrek M. CCL5/RANTES gene polymorphisms in Slavonic patients with myocardial infarction. Mediators Inflamm. 2011;2011:525691.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M, ESC Committee for Practice Guidelines (CPG). Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2008;23:2909–45.

    Google Scholar 

  41. van Loosdregt J, van Oosterhout MF, Bruggink AH, van Wichen DF, van Kuik J, de Koning E, Baan CC, de Jonge N, Gmelig-Meyling FH, de Weger RA. The chemokine and chemokine receptor profile of infiltrating cells in the wall of arteries with cardiac allograft vasculopathy is indicative of a memory T-helper 1 response. Circulation. 2006;114:1599–607.

    Article  PubMed  Google Scholar 

  42. Virani SS, Nambi V, Hoogeveen R, Wasserman BA, Coresh J, Gonzalez F 2nd, Chambless LE, Mosley TH, Boerwinkle E, Ballantyne CM. Relationship between circulating levels of RANTES (regulated on activation, normal T-cell expressed, and secreted) and carotid plaque characteristics: the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study. Eur Heart J. 2011;32:459–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Vogiatzi K, Voudris V, Apostolakis S, Kochiadakis GE, Thomopoulou S, Zaravinos A, Spandidos DA. Genetic diversity of RANTES gene promoter and susceptibility to coronary artery disease and restenosis after percutaneous coronary intervention. Thromb Res. 2009;124:84–9.

    Article  CAS  PubMed  Google Scholar 

  44. von Hundelshausen P, Weber KS, Huo Y, Proudfoot AE, Nelson PJ, Ley K, Weber C. RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation. 2001;103:1772–7.

    Article  Google Scholar 

  45. Weinberg EO, Shimpo M, De Keulenaer GW, MacGillivray C, Tominaga S, Solomon S, Rouleau JL, Lee RT. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation. 2002;106:2961–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Weinberg EO, Shimpo M, Hurwitz S, Tominaga S, Rouleau JL, Lee RT. Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation. 2003;107:721–6.

    Article  PubMed  Google Scholar 

  47. Yun JJ, Fischbein MP, Laks H, Irie Y, Espejo ML, Fishbein MC, Berliner JA, Ardehali A. Rantes production during development of cardiac allograft vasculopathy. Transplantation. 2001;71:1649–56.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors alone are responsible for the content and writing of this article. This work was supported by the Project MUNI/A/1003/2013, the Project of Conceptual Development of Research Organization (Department of Health) 65269705 (University Hospital Brno) and by the European Regional Development Fund—Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123).

Conflict of interest

The authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Faculty of Medicine, Institute of Pathological Physiology, Masaryk University, Kamenice 753/5, 625 00, Brno, Czech Republic

    Jolana Lipkova, Kamil Duris, Anna Vasku & Monika Goldbergova Pavkova

  2. Department of Internal Cardiology Medicine, University Hospital Brno, Jihlavska 20, 625 00, Brno, Czech Republic

    Jiri Parenica, Katerina Helanova & Lenka Kubkova

  3. Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic

    Jiri Parenica, Katerina Helanova & Lenka Kubkova

  4. Department of Cardiovascular Disease, International Clinical Research Center, University Hospital St Anne’s, Pekarska 53, 656 91, Brno, Czech Republic

    Jiri Parenica & Lenka Kubkova

  5. Department of Biochemistry, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic

    Josef Tomandl

Authors
  1. Jolana Lipkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiri Parenica
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kamil Duris
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katerina Helanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Josef Tomandl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lenka Kubkova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anna Vasku
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Monika Goldbergova Pavkova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Monika Goldbergova Pavkova.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lipkova, J., Parenica, J., Duris, K. et al. Association of circulating levels of RANTES and −403G/A promoter polymorphism to acute heart failure after STEMI and to cardiogenic shock. Clin Exp Med 15, 405–414 (2015). https://doi.org/10.1007/s10238-014-0294-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-014-0294-5

Keywords

Search

Navigation