Evidence map›Paper›PMID 17492053›Full record

ArticleThe Journal of clinical investigation2007

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

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

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05335629 (Evaluation of the Effect of Dapagliflozin on Cardiac Remodeling in Post Myocardial Infarction Patients), which is not on this map. Cited by 489 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
489citing papers in PubMed, 4 pooled it
10.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05335629 nacompletedstarted 2022, after this paper: background citation

Evaluation of the Effect of Dapagliflozin on Cardiac Remodeling in Post Myocardial Infarction Patients

Ran2022Enrolled54Registered outcomes2Posted comparisons0ConditionsDiabetes Mellitus, Type 2, Myocardial Infarction, Myocardial Remodeling, VentricularArmsDapagliflozin 10mg Tab
PMID 29153199PMID 10491084PMID 12460879PMID 15110792PMID 15226248PMID 16286016PMID 17692745PMID 21943940PMID 2532153PMID 25464491PMID 25748771PMID 26615096other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

489 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,017 citations in OpenAlex.

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  5. Evaluating the role of montelukast on doxorubicin-induced cardiotoxicity in breast cancer patients.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025
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429 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Shoji SanadaCardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Daihiko Hakuno
Luke J Higgins
Eric R Schreiter
Andrew N J McKenzie
Richard T Lee
Harvard University · USBrigham and Women's Hospital · USMRC Laboratory of Molecular Biology · GB

Funding

Endothelial-Cardiomyocyte Interactions and AssemblyR01HL081404 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LEE, RICHARD T · 2005 to 2008
$1.9M
Medical Research Council MC_U105178805NHLBI NIH HHS R01 HL081404NHLBI NIH HHS R01HL081404
6 · The paper itself

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-kappaB, it inhibited angiotensin II- and phenylephrine-induced phosphorylation of inhibitor of NF-kappa B alpha (I kappa B alpha) and NF-kappaB 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.

Indexed as

AnimalsBiomechanical PhenomenaCardiotonic AgentsCells, CulturedFibroblastsHumansInterleukin-1 Receptor-Like 1 ProteinInterleukin-33InterleukinsMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacNF-kappa BRatsCardiotonic AgentsIL1RL1 protein, humanIl1rl1 protein, mouseIL33 protein, humanIl33 protein, mouseInterleukin-1 Receptor-Like 1 ProteinInterleukin-33InterleukinsMembrane ProteinsNF-kappa BReceptors, Cell SurfaceReceptors, InterleukinRecombinant Proteins

Identifiers

PMID17492053
PMCPMC1865027
OpenAlexW2048813343

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.