Skip to main content

Advertisement

SpringerLink
Log in

ST2: A Novel Remodeling Biomarker in Acute and Chronic Heart Failure

  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

ST2, a member of the interleukin-1 receptor family, is a novel biomarker of mechanical stress measurable in serum that has been shown in animal and in vitro models to be physiologically linked to cardiac hypertrophy, fibrosis, and ventricular dysfunction. In patients with acute myocardial infarction and heart failure (HF), an elevated serum level of the soluble isoform of ST2 is associated with an increased risk of mortality or future HF, independent of natriuretic peptides, and correlates with markers of ventricular structure and function. In acute HF, elevated soluble ST2 levels strongly associate with the presence and severity of the disease and forecast short- and long-term mortality independent of other traditional clinical, biochemical, and echocardiographic markers of risk. This review discusses the biology and physiology of ST2, as well as its implications on the pathogenesis and prognosis of patients with acute coronary syndromes or acute and chronic HF syndromes.

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

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Daniels L, Maisel AS: Natriuretic peptides. J Am Coll Cardiol 2007, 50:2357–2368.

    Article  CAS  PubMed  Google Scholar 

  2. Liang F, Gardner DG: Mechanical strain activates BNP gene transcription through a p38/NF-κB-dependent mechanism. J Clin Invest 1999, 101:1603–1612.

    Article  Google Scholar 

  3. Fonarow GC, Peacock WF, Phillips CO, et al.: Admission B-type natriuretic peptide levels and in-hospital mortality in acute decompensated heart failure. J Am Coll Cardiol 2007, 49:1943–1950.

    Article  CAS  PubMed  Google Scholar 

  4. Chen AA, Wood MJ, Krauser DG, et al.: NT-proBNP levels, echocardiographic findings, and outcomes in breathless patients: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) echocardiographic substudy. Eur Heart J 2006, 27:839–845.

    Article  CAS  PubMed  Google Scholar 

  5. Bettencourt P, Ferreira S, Azevedo A, Ferreira A: Preliminary data on the potential usefulness of B-type natriuretic peptide levels in predicting outcome after hospital discharge in patients with heart failure. Am J Med 2002, 113:215–219.

    Article  CAS  PubMed  Google Scholar 

  6. Logeart D, Thabut G, Jourdain P, et al.: Predischarge B-type natriuretic peptide assay for identifying patients at high risk for re-admission after decompensated heart failure. J Am Coll Cardiol 2004, 43:635–641.

    Article  CAS  PubMed  Google Scholar 

  7. Weinberg EO, Shimpo M, De Keulenaer GW, et al.: Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation 2002, 106:2961–2966.

    Article  CAS  PubMed  Google Scholar 

  8. Sabatine MS, Morrow DA, Higgins LJ, et al.: Complementary roles for biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction. Circulation 2008, 117:1936–1944.

    Article  CAS  PubMed  Google Scholar 

  9. Shimpo M, Morrow DA, Weinberg EO, et al.: Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction. Circulation 2004, 109:2186–2190.

    Article  CAS  PubMed  Google Scholar 

  10. Weinberg EO, Shimpo M, Hurwitz S, et al.: Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation 2003, 107:721–726.

    Article  PubMed  Google Scholar 

  11. Rehman SU, Mueller T, Januzzi JL Jr: Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure. J Am Coll Cardiol 2008, 52:1458–1465.

    Article  CAS  PubMed  Google Scholar 

  12. Januzzi JL Jr, Peacock WF, Maisel AS, et al.: Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE study. J Am Coll Cardiol 2007, 50:607–613.

    Article  CAS  PubMed  Google Scholar 

  13. Myeller T, et al.: Increased plasma concentrations of soluble ST2 are predictive for 1-year mortality in patients with acute destabilized heart failure. Clin Chem 2008, S4:752–756.

    Article  Google Scholar 

  14. Iwahana H, Yanagisawa K, Ito-Kosaka A, et al.: Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells. Eur J Biochem 1999, 264:397–406.

    Article  CAS  PubMed  Google Scholar 

  15. Coyle AJ, Lloyd C, Tian J, et al.: Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses. J Exp Med 1999, 190:895–902.

    Article  CAS  PubMed  Google Scholar 

  16. •• Sanada S, Hakuno D, Higgins LJ, et al.: IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest 2007, 117:1538–1549. This report extensively details the relationship between ST2 and IL-33 in in vitro and in vivo model, providing a potential mechanism for elevated ST2 concentrations in adverse cardiac remodeling.

    Article  CAS  PubMed  Google Scholar 

  17. Seki K, Sanada S, Kudinova AY, et al.: Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail 2009, 2:684–691.

    Article  CAS  PubMed  Google Scholar 

  18. Mueller T, Dieplinger B, Gegenhuber A, et al.: Increased plasma concentrations of soluble ST2 are predictive for 1-year mortality in patients with acute destabilized heart failure. Clin Chem 2008, S4:752–756.

    Article  Google Scholar 

  19. •• Shah RV, Chen-Tournoux AA, Picard MH, et al.: Serum levels of the interleukin- 1 receptor family member ST2, cardiac structure and function, and long-term mortality in patients with acute dyspnea. Circulation: Heart Failure 2009, 2:311–319. This is an echocardiographic analysis of the PRIDE study that details the significant relationships between sST2 level and markers of right ventricular and left ventricular systolic and diastolic function, as well as the long-term prognostic import of an elevated admission sST2 level.

    Article  CAS  Google Scholar 

  20. Bayés-Genís A, Santaló-Bel M, Zapico-Muñiz E, et al.: N-terminal pro-brain natriuretic peptide (NT-proBNP) in the emergency diagnosis and in-hospital monitoring of patients with dyspnoea and ventricular dysfunction. Eur J Heart Fail 2004, 6:301–308.

    Article  PubMed  Google Scholar 

  21. Jourdain P, Jondeau G, Funck F, et al.: Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP Multicenter Study. J Am Coll Cardiol 2007, 49:1733–1739.

    Article  CAS  PubMed  Google Scholar 

  22. Pfisterer M, Buser P, Rickli H, et al.: BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial. JAMA 2009, 301:383–392.

    Article  CAS  PubMed  Google Scholar 

  23. Shah M: STARBRITE: A randomized pilot trial of BNP-guided therapy in patients with advanced heart failure. Circulation 2006, 114:II528.

    Google Scholar 

  24. Troughton RW, Frampton CM, Yandle TG, et al.: Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 2000, 355:1126–1130.

    Article  CAS  PubMed  Google Scholar 

  25. Boisot S, et al.: Serial sampling of ST2 predicts 90-day mortality following destabilized heart failure. J Card Fail 2008, 14:732–738.

    Article  PubMed  Google Scholar 

  26. Bartunek J, Delrue L, Van Durme F, et al.: Nonmyocardial production of ST2 protein in human hypertrophy and failure is related to diastolic load. J Am Coll Cardiol 2008, 52:2166–2174.

    Article  CAS  PubMed  Google Scholar 

  27. •• Dieplinger B, Januzzi JL Jr, Steinmair M, et al.: Analytical and clinical evaluation of a novel high-sensitivity assay for measurement of soluble ST2 in human plasma—The Presage ST2 assay. Clinica Chimica Acta 2009, 409:33–40. This report details a novel, high-sensitivity assay used to measure ST2 concentrations.

    Article  CAS  Google Scholar 

Download references

Disclosure

Dr. Januzzi has received grants from Critical Diagnostics, Roche, and Siemens.

No further potential conflict of interest relevant to this article was reported.

Author information

Authors and Affiliations

  1. Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA

    Ravi V. Shah & James L. Januzzi Jr

Authors
  1. Ravi V. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James L. Januzzi Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James L. Januzzi Jr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shah, R.V., Januzzi, J.L. ST2: A Novel Remodeling Biomarker in Acute and Chronic Heart Failure. Curr Heart Fail Rep 7, 9–14 (2010). https://doi.org/10.1007/s11897-010-0005-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11897-010-0005-9

Keywords

Search

Navigation