Evidence map›Paper›PMID 22675198›Full record

ArticleClinical chemistry2012

Identification of follistatin-like 1 by expression cloning as an activator of the growth differentiation factor 15 gene and a prognostic biomarker in acute coronary syndrome.

Christian Widera, Evangelos Giannitsis, Tibor Kempf, Mortimer Korf-Klingebiel, Beate Fiedler, Sarita Sharma, Hugo A Katus, Yasuhide Asaumi, Masayuki Shimano, Kenneth Walsh and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.2field-weighted citation impact, top 8% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Novel Circulating Biomarkers in Aortic Valve Stenosis.International journal of molecular sciences · 2025
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. GDF15 and Cardiac Cells: Current Concepts and New Insights.International journal of molecular sciences · 2021
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Follistatin-like 1 in development and human diseases.Cellular and molecular life sciences : CMLS · 2018
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. [Change in serum follistatin-like protein 1 and its clinical significance in children with chronic heart failure].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2016
    Article
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

11 authors at 3 institutions in 2 countries.

Christian WideraDivision of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany;
Evangelos Giannitsis
Tibor Kempf
Mortimer Korf-Klingebiel
Beate Fiedler
Sarita Sharma
Hugo A Katus
Yasuhide Asaumi
Masayuki Shimano
Kenneth Walsh
Kai C Wollert
Medizinische Hochschule Hannover · DEBoston University · USHeidelberg University · DE

Funding

Redox regulation in Endothelial Progenitor CellsP01HL081587 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WALSH, KENNETH · 2005 to 2015
$21.5M
SIRT1, Polyphenols, and Endothelial OxidantsP01HL068758 · NHLBI · BOSTON MEDICAL CENTER · PI WALSH, KENNETH · 2003 to 2013
$14.1M
REGULATION OF VESSEL WALL APOPTOSISR37AG015052 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WALSH, KENNETH · 2003 to 2012
$4.0M
Muscle loss and metabolic dysfunction associated with agingR01AG034972 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WALSH, KENNETH · 2010 to 2014
$1.6M
Paracrine Regulation of Heart FailureR01HL116591 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WALSH, KENNETH · 2013 to 2016
$1.6M
NHLBI NIH HHS P01 HL068758NHLBI NIH HHS P01 HL081587NHLBI NIH HHS R01 HL116591NIA NIH HHS R01 AG034972NIA NIH HHS R37 AG015052
6 · The paper itself

Abstract

backgroundGrowth differentiation factor 15 (GDF15) is a stress-responsive cytokine and biomarker that is produced after myocardial infarction and that is related to prognosis in acute coronary syndrome (ACS). We hypothesized that secreted proteins that activate GDF15 production may represent new ACS biomarkers.

methodsWe expressed clones from an infarcted mouse heart cDNA library in COS1 cells and assayed for activation of a luciferase reporter gene controlled by a 642-bp fragment of the mouse growth differentiation factor 15 (GDF15) gene promoter. We measured the circulating concentrations of follistatin-like 1 (FSTL1) and GDF15 in 1369 patients with ACS.

resultsOne cDNA clone that activated the GDF15 promoter-luciferase reporter encoded the secreted protein FSTL1. Treatment with FSTL1 activated GDF15 production in cultured cardiomyocytes. Transgenic production of FSTL1 stimulated GDF15 production in the murine heart, whereas cardiomyocyte-selective deletion of FSTL1 decreased production of GDF15 in cardiomyocytes, indicating that FSTL1 is sufficient and required for GDF15 production. In ACS, FSTL1 emerged as the strongest independent correlate of GDF15 (partial R(2) = 0.26). A total of 106 patients died of a cardiovascular cause during a median follow-up of 252 days. Patients with an FSTL1 concentration in the top quartile had a 3.7-fold higher risk of cardiovascular death compared with patients in the first 3 quartiles (P < 0.001). FSTL1 remained associated with cardiovascular death after adjustment for clinical, angiographic, and biochemical variables.

conclusionsOur study is the first to use expression cloning for biomarker discovery upstream of a gene of interest and to identify FSTL1 as an independent prognostic biomarker in ACS.

Indexed as

Acute Coronary SyndromeAnimalsBiomarkersCloning, MolecularFollistatin-Related ProteinsGene Expression ProfilingGrowth Differentiation Factor 15HumansMiceMice, TransgenicMyocardial InfarctionMyocardiumMyocytes, CardiacPrognosisPromoter Regions, GeneticRisk AssessmentBiomarkersFollistatin-Related ProteinsGdf15 protein, mouseGrowth Differentiation Factor 15

Identifiers

PMID22675198
PMCPMC3539794
OpenAlexW2121006731

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Registered trials

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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 OpenQuestion graph.