Evidence map›Paper›PMID 20124440›Full record

ArticleCirculation. Cardiovascular genetics2010

Heart failure-associated changes in RNA splicing of sarcomere genes.

Sek Won Kong, Yong Wu Hu, Joshua W K Ho, Sadakatsu Ikeda, Sean Polster, Ranjit John, Jennifer L Hall, Egbert Bisping, Burkert Pieske, Cristobal G dos Remedios and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation. Cardiovascular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

115 citing papers in PubMed, 183 citations in OpenAlex.

  1. Review
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  8. Integrative transcriptomic analysis reveals alternative splicing programs in sepsis-induced myocardial injury across dual mouse models.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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  17. mRNA Isoforms and Variants in Health and Disease.International journal of molecular sciences · 2025
    Review
  18. Article
  19. Article
  20. Article

55 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

11 authors at 6 institutions in 4 countries.

Sek Won KongDepartment of Cardiology, Children's Hospital Boston, Mass, USA.
Yong Wu Hu
Joshua W K Ho
Sadakatsu Ikeda
Sean Polster
Ranjit John
Jennifer L Hall
Egbert Bisping
Burkert Pieske
Cristobal G dos Remedios
William T Pu
Data61 · AURobert Bosch (Australia) · AUUniversity of Sydney · AUWenzhou Medical University · CNMedical University of Graz · ATUniversity of Minnesota · US

Funding

HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2M
Progenitor Cells inHuman Skeletal MuscleP50NS040828 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI KOHANE, ISAAC S. · 2008 to 2011
$5.9M
Genome-wide discovery of alternative splicing in human heart failureR21HL089417 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI PU, WILLIAM TSWENCHING · 2007 to 2009
$600k
NCRR NIH HHS UL1 RR025758NHLBI NIH HHS R21 HL089417NHLBI NIH HHS R21HL89417NICHD NIH HHS P30 HD018655NICHD NIH HHS P30 HD18655NINDS NIH HHS P50 NS040828NINDS NIH HHS P50 NS40828
6 · The paper itself

Abstract

backgroundAlternative mRNA splicing is an important mechanism for regulation of gene expression. Altered mRNA splicing occurs in association with several types of cancer, and a small number of disease-associated changes in splicing have been reported in heart disease. However, genome-wide approaches have not been used to study splicing changes in heart disease. We hypothesized that mRNA splicing is different in diseased hearts compared with control hearts. METHODS AND

resultsWe used the Affymetrix Exon array to globally evaluate mRNA splicing in left ventricular myocardial RNA from controls (n=15) and patients with ischemic cardiomyopathy (n=15). We observed a broad and significant decrease in mRNA splicing efficiency in heart failure, which affected some introns to a greater extent than others. The profile of mRNA splicing separately clustered ischemic cardiomyopathy and control samples, suggesting distinct changes in mRNA splicing between groups. Reverse transcription-polymerase chain reaction validated 9 previously unreported alternative splicing events. Furthermore, we demonstrated that splicing of 4 key sarcomere genes, cardiac troponin T (TNNT2), cardiac troponin I (TNNI3), myosin heavy chain 7 (MYH7), and filamin C, gamma (FLNC), was significantly altered in ischemic cardiomyopathy and in dilated cardiomyopathy and aortic stenosis. In aortic stenosis samples, these differences preceded the onset of heart failure. Remarkably, the ratio of minor to major splice variants of TNNT2, MYH7, and FLNC classified independent test samples as control or disease with >98% accuracy.

conclusionsOur data indicate that mRNA splicing is broadly altered in human heart disease and that patterns of aberrant RNA splicing accurately assign samples to control or disease classes.

Indexed as

RNA SplicingAortic Valve StenosisCardiomyopathy, DilatedComputational BiologyContractile ProteinsExonsFilaminsHeart FailureHeart VentriclesHumansMicrofilament ProteinsMyocardial IschemiaMyosin Heavy ChainsSarcomeresTroponin ITroponin TContractile ProteinsFilaminsFLNC protein, humanMicrofilament ProteinsMyosin Heavy ChainsTNNT2 protein, humanTroponin ITroponin T

Identifiers

PMID20124440
PMCPMC3073230
OpenAlexW2008929866

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.