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Citations to this article

IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system
Shoji Sanada, … , Andrew N.J. McKenzie, Richard T. Lee
Shoji Sanada, … , Andrew N.J. McKenzie, Richard T. Lee
Published June 1, 2007
Citation Information: J Clin Invest. 2007;117(6):1538-1549. https://doi.org/10.1172/JCI30634.
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Research Article Cardiology Article has an altmetric score of 10

IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system

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Abstract

ST2 is an IL-1 receptor family member with transmembrane (ST2L) and soluble (sST2) isoforms. sST2 is a mechanically induced cardiomyocyte protein, and serum sST2 levels predict outcome in patients with acute myocardial infarction or chronic heart failure. Recently, IL-33 was identified as a functional ligand of ST2L, allowing exploration of the role of ST2 in myocardium. We found that IL-33 was a biomechanically induced protein predominantly synthesized by cardiac fibroblasts. IL-33 markedly antagonized angiotensin II– and phenylephrine-induced cardiomyocyte hypertrophy. Although IL-33 activated NF-κB, it inhibited angiotensin II– and phenylephrine-induced phosphorylation of inhibitor of NF-κBα (IκBα) and NF-κB nuclear binding activity. sST2 blocked antihypertrophic effects of IL-33, indicating that sST2 functions in myocardium as a soluble decoy receptor. Following pressure overload by transverse aortic constriction (TAC), ST2–/– mice had more left ventricular hypertrophy, more chamber dilation, reduced fractional shortening, more fibrosis, and impaired survival compared with WT littermates. Furthermore, recombinant IL-33 treatment reduced hypertrophy and fibrosis and improved survival after TAC in WT mice, but not in ST2–/– littermates. Thus, IL-33/ST2 signaling is a mechanically activated, cardioprotective fibroblast-cardiomyocyte paracrine system, which we believe to be novel. IL-33 may have therapeutic potential for beneficially regulating the myocardial response to overload.

Authors

Shoji Sanada, Daihiko Hakuno, Luke J. Higgins, Eric R. Schreiter, Andrew N.J. McKenzie, Richard T. Lee

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 9 29 35 35 36 43 33 28 25 26 25 19 30 22 14 14 8 11 442
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Citations to this article in year 2020 (43)

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Angiotensin Converting Enzyme Inhibitors (ACEIs) Decrease the Progression of Cardiac Fibrosis in Rheumatic Heart Disease Through the Inhibition of IL-33/sST2
AM Ambari, B Setianto, A Santoso, B Radi, B Dwiputra, E Susilowati, F Tulrahmi, PA Doevendans, MJ Cramer
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Mesenchymal-endothelial transition-derived cells as a potential new regulatory target for cardiac hypertrophy
W Dong, R Li, H Yang, Y Lu, L Zhou, L Sun, D Wang, J Duan
Scientific Reports 2020
Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation
Y Wang, F Yao, L Wang, Z Li, Z Ren, D Li, M Zhang, L Han, S Wang, B Zhou, L Wang
Nature Communications 2020
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Heart Failure Reviews 2020
IL33 and Mast Cells—The Key Regulators of Immune Responses in Gastrointestinal Cancers?
MF Eissmann, M Buchert, M Ernst
Frontiers in immunology 2020

The Contradictory Role of Interleukin-33 in Immune Cells and Tumor Immunity


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Interleukin-36 Cytokine/Receptor Signaling: A New Target for Tissue Fibrosis
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Crosstalk between cardiomyocytes and noncardiomyocytes is essential to prevent cardiomyocyte apoptosis induced by proteasome inhibition
F Guo, CC Zhang, , T Li, CH Fang,
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The pro-inflammatory marker soluble suppression of tumorigenicity-2 (ST2) is reduced especially in diabetic morbidly obese patients undergoing bariatric surgery
S Demyanets, C Kaun, A Kaider, W Speidl, M Prager, S Oravec, P Hohensinner, J Wojta, G Rega-Kaun
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NN Shah, P Ayyadurai, M Saad, CE Kosmas, MU Dogar, U Patel, TJ Vittorio
JRSM cardiovascular disease 2020
The association between soluble suppression of tumorigenicity-2 and long-term prognosis in patients with coronary artery disease: A meta-analysis
N Liu, T Hang, X Gao, W Yang, W Kong, Q Lou, J Yang, V Lionetti
PloS one 2020

Biomarkers of IL-33 and sST2 and Lack of Association with Carvedilol Therapy in Heart Failure


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D Ojji, E Libhaber, K Lamont, F Thienemann, K Sliwa
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Suppression of Tumourigenicity 2 in Heart Failure With Preserved Ejection Fraction
V Zach, FL Bähr, F Edelmann
Cardiac Failure Review 2020
Association of soluble ST2 with all-cause and cardiovascular mortality in renal transplant recipients: a single-centre cohort study
PA Devine, C Cardwell, AP Maxwell
BMC Nephrology 2020
Association of plasma-soluble ST2 and galectin-3 with cardiovascular events and mortality following cardiac surgery
DM Patel, H Thiessen-Philbrook, JR Brown, E McArthur, DG Moledina, SG Mansour, MG Shlipak, JL Koyner, P Kavsak, RP Whitlock, AD Everett, DJ Malenka, AX Garg, SG Coca, CR Parikh
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Innate Lymphoid Cells Play a Pathogenic Role in Pericarditis
HS Choi, T Won, X Hou, G Chen, W Bracamonte-Baran, MV Talor, I Jurčová, O Szárszoi, L Čurnova, I Stříž, JE Hooper, V Melenovský, D Čiháková
Cell Reports 2020
Nociceptor Interleukin 33 Receptor/ST2 Signaling in Vibration-Induced Muscle Pain in the Rat
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The journal of pain : official journal of the American Pain Society 2020
Human Immunodeficiency Virus–Associated Myocardial Diastolic Dysfunction and Soluble ST2 Concentration in Tanzanian Adults: A Cross-Sectional Study
JR Kingery, P Goyal, R Hosalli, MH Lee, B Desderius, F Kalokola, A Makubi, S Fadhil, S Kapiga, D Karmali, D Kaminstein, R Devereux, M McNairy, W Johnson, D Fitzgerald, R Peck
The Journal of Infectious Diseases 2020
Endothelin-1, cardiac morphology, and heart failure: the MESA angiogenesis study
PJ Leary, NS Jenny, DA Bluemke, SM Kawut, RA Kronmal, JA Lima, BA Maron, DD Ralph, SG Rayner, JJ Ryan, ZL Steinberg, KD Stukovsky, RJ Tedford
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2020
Time-dependent, dynamic prediction of fatty acid-binding protein 4, Galectin-3, and soluble ST2 measurement with poor outcome after acute stroke
C Hansen, C Sastre, Z Wolcott, MB Bevers, WT Kimberly
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Are existing and emerging biomarkers associated with cardiorespiratory fitness in patients with chronic heart failure?
M Fudim, JP Kelly, AD Jones, OF AbouEzzeddine, AP Ambrosy, SJ Greene, YN Reddy, KJ Anstrom, B Alhanti, GD Lewis, AF Hernandez, GM Felker
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Association of Soluble Suppression of Tumorigenesis 2 (sST2) With Platelet Activation, Monocyte Tissue Factor and Ischemic Outcomes Following Angioplasty and Stenting
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E Vianello, E Dozio, F Bandera, M Froldi, E Micaglio, J Lamont, L Tacchini, G Schmitz, MM Romanelli
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Soluble ST2 is associated with increased carotid intima-media thickness in patients with type 2 diabetes mellitus: A case-control study
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Serum ST2 and hospitalization rates in Caucasian and African American outpatients with heart failure
P Savvoulidis, JV Snider, S Rawal, AA Morris, J Butler, VV Georgiopoulou, AP Kalogeropoulos
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Serum soluble suppression of tumorigenicity-2 level associates with severity of pulmonary hypertension associated with uncorrected atrial septal defect
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