title: ST2 as a cardiovascular risk biomarker: from the bench to the bedside.
abstract: ST2 is a member of the interleukin (IL)-1 receptor family discovered in a classical translational science fashion, and exists in two forms, a trans-membrane receptor (ST2L) as well as a soluble decoy receptor (sST2). The ligand of ST2 is IL-33, which is involved in reducing fibrosis and hypertrophy in mechanically strained tissues. In in vitro and in vivo models, ST2L transduces the effects of IL-33, while excess sST2 or abnormalities in ST2 signaling leads to cardiac hypertrophy, fibrosis, and ventricular dysfunction. Clinically, in patients with symptomatic heart failure (HF), elevated concentrations of sST2 are strongly associated with severity of the diagnosis, and powerfully predict increased risk of complications, independent of other established or emerging biomarkers. sST2 testing has also been shown to predict onset of symptomatic HF in patients with acute myocardial infarction, while in community-based subjects, sST2 values independently predict future HF, cardiovascular disease events, and mortality.
authors.affiliation: Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 32 Fruit Street, Yawkey 5984, Boston, MA 02114, USA. jjanuzzi@partners.org
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011237:Predictive Value of Tests; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood*; D012307:Risk Factors; D012720:Severity of Illness Index; D057170:Translational Research, Biomedical; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface
references.citation: Circulation. 2008 Apr 15;117(15):1936-44
references.pmid: 18378613
references.citation: Circulation. 2003 Feb 11;107(5):721-6
references.pmid: 12578875
references.citation: J Exp Med. 2008 Feb 18;205(2):339-46
references.pmid: 18268038
references.citation: J Am Coll Cardiol. 2007 Dec 18;50(25):2357-68
references.pmid: 18154959
references.citation: Am J Clin Pathol. 2008 Oct;130(4):578-84
references.pmid: 18794051
references.citation: Circulation. 2004 May 11;109(18):2186-90
references.pmid: 15117853
references.citation: Eur J Heart Fail. 2011 Jul;13(7):718-25
references.pmid: 21551163
references.citation: Circulation. 2012 Sep 25;126(13):1596-604
references.pmid: 22907935
references.citation: J Am Coll Cardiol. 2011 Oct 25;58(18):1881-9
references.pmid: 22018299
references.citation: Nat Immunol. 2004 Apr;5(4):373-9
references.pmid: 15004556
references.citation: Clin Chim Acta. 2009 Nov;409(1-2):33-40
references.pmid: 19699192
references.citation: Am J Cardiol. 2011 Jan 15;107(2):259-67
references.pmid: 21211603
references.citation: Clin Chem. 2010 Dec;56(12):1814-21
references.pmid: 20921266
references.citation: Arch Intern Med. 2006 Feb 13;166(3):315-20
references.pmid: 16476871
references.citation: Circ Heart Fail. 2011 Mar;4(2):180-7
references.pmid: 21178018
references.citation: J Immunol. 2010 May 15;184(10):5802-8
references.pmid: 20400705
references.citation: J Am Coll Cardiol. 2009 Dec 1;54(23):2174-9
references.pmid: 19942089
references.citation: Crit Care. 2012 Jul 25;16(4):R135
references.pmid: 22830581
references.citation: Am J Respir Crit Care Med. 2001 Jul 15;164(2):277-81
references.pmid: 11463601
references.citation: J Card Fail. 2008 Nov;14(9):732-8
references.pmid: 18995177
references.citation: J Am Coll Cardiol. 2007 Aug 14;50(7):607-13
references.pmid: 17692745
references.citation: J Am Coll Cardiol. 2008 Oct 28;52(18):1458-65
references.pmid: 19017513
references.citation: J Clin Invest. 2007 Jun;117(6):1538-49
references.pmid: 17492053
references.citation: N Engl J Med. 2008 May 15;358(20):2148-59
references.pmid: 18480207
references.citation: J Am Coll Cardiol. 2010 Jan 19;55(3):243-50
references.pmid: 20117403
references.citation: Clin Chem. 2008 Apr;54(4):752-6
references.pmid: 18375488
references.citation: Clin Chem. 2012 Dec;58(12):1673-81
references.pmid: 23065477
references.citation: Circulation. 2004 Oct 12;110(15):2168-74
references.pmid: 15451800
references.citation: Circulation. 2002 Dec 3;106(23):2961-6
references.pmid: 12460879
references.citation: Circ Heart Fail. 2009 Nov;2(6):684-91
references.pmid: 19919994
references.citation: J Exp Med. 1999 Oct 4;190(7):895-902
references.pmid: 10510079
references.citation: Eur Heart J. 2006 Apr;27(7):839-45
references.pmid: 16510467
references.citation: Clin Chem. 2012 Jan;58(1):257-66
references.pmid: 22096031
references.citation: Cardiology. 2012;122(3):158-66
references.pmid: 22832599
references.citation: Clin Chem. 2012 Jan;58(1):127-38
references.pmid: 22086968
references.citation: Eur J Biochem. 1999 Sep;264(2):397-406
references.pmid: 10491084
references.citation: J Immunol. 2008 Jul 1;181(1):62-72
references.pmid: 18566370
references.citation: Circ Heart Fail. 2009 Jul;2(4):311-9
references.pmid: 19808354
references.citation: Transplantation. 2010 May 27;89(10):1189-97
references.pmid: 20220570