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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: 8 29 35 35 36 43 33 28 25 26 25 19 30 22 14 14 8 11 441
Citation information
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Citations to this article in year 2010 (14)

Title and authors Publication Year
Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice
AM Miller, DL Asquith, AJ Hueber, LA Anderson, WM Holmes, AN McKenzie, D Xu, N Sattar, IB McInnes, FY Liew
Circulation research 2010
Identification and functionality of proteomes secreted by rat cardiac stem cells and neonatal cardiomyocytes
M Stastna, I Chimenti, E Marbán, JE van Eyk
PROTEOMICS 2010
Intramyocardial fibroblast myocyte communication
R Kakkar, RT Lee
Circulation research 2010
Early detection of myocardial dysfunction and heart failure
G de Couto, M Ouzounian, PP Liu
Nature Reviews Cardiology 2010
Soluble ST2 plasma concentrations predict mortality in severe sepsis
JJ Hoogerwerf, MW Tanck, MA van Zoelen, X Wittebole, PF Laterre, T der Poll
Intensive Care Medicine 2010
Synovial fibroblasts promote the expression and granule accumulation of tryptase via interleukin-33 and its receptor ST-2 (IL1RL1)
S Kaieda, K Shin, PA Nigrovic, K Seki, RT Lee, RL Stevens, DM Lee
The Journal of biological chemistry 2010
Biomarkers in acute myocardial infarction
D Chan, LL Ng
BMC Medicine 2010
Expression and regulation of interleukin-33 in human monocytes
CJ Nile, E Barksby, P Jitprasertwong, PM Preshaw, JJ Taylor
Immunology 2010
Disease-associated functions of IL-33: the new kid in the IL-1 family
FY Liew, NI Pitman, IB McInnes
Nature Reviews Immunology 2010
ST2: A Novel Remodeling Biomarker in Acute and Chronic Heart Failure
RV Shah, JL Januzzi
Current Heart Failure Reports 2010
The enigmatic processing and secretion of interleukin-33
W Zhao, Z Hu
Cellular and Molecular Immunology 2010
Genetic variability of the distal promoter of the ST2 gene is associated with angiographic severity of coronary artery disease
A Tsapaki, A Zaravinos, S Apostolakis, K Voudris, K Vogiatzi, GE Kochiadakis, DA Spandidos
Journal of Thrombosis and Thrombolysis 2010
Inflammatory Bowel Disease-Associated Interleukin-33 Is Preferentially Expressed in Ulceration-Associated Myofibroblasts
J Sponheim, J Pollheimer, T Olsen, J Balogh, C Hammarström, T Loos, M Kasprzycka, DR Sørensen, HR Nilsen, AM Küchler, MH Vatn, G Haraldsen
The American Journal of Pathology 2010
Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis
A Kobori, Y Yagi, H Imaeda, H Ban, S Bamba, T Tsujikawa, Y Saito, Y Fujiyama, A Andoh
Journal of Gastroenterology 2010

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