Evidence map›Paper›PMID 24429688›Full record

ArticleCirculation2014

Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support.

Kai-Chien Yang, Kathryn A Yamada, Akshar Y Patel, Veli K Topkara, Isaac George, Faisal H Cheema, Gregory A Ewald, Douglas L Mann, Jeanne M Nerbonne

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 278 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
278citing papers in PubMed, 4 pooled it
–field-weighted citation impact
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

278 citing papers in PubMed, 4 syntheses or guidelines pooled it.

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  10. Are RNA Therapies a Solid Foundation or a Frontier Yet to Be Conquered?International journal of molecular sciences · 2026
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218 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Kai-Chien YangDepartment of Developmental Biology (K.-C.Y., J.M.N.) and Center for Cardiovascular Research, Division of Cardiology, Department of Internal Medicine (K.A.Y., A.Y.P., V.K.T., G.A.E., D.L.M.), Washington University Medical School, St. Louis, MO; Division of Cardiothoracic Surgery, New York Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY (I.G.); and Department of Surgery, University of Maryland School of Medicine, Baltimore (F.H.C.). Dr Yang's current affiliation is the Department of Pharmacology, National Taiwan University School of Medicine, Taipei, Taiwan.
Kathryn A Yamada
Akshar Y Patel
Veli K Topkara
Isaac George
Faisal H Cheema
Gregory A Ewald
Douglas L Mann
Jeanne M Nerbonne

Funding

Washington University Institute of Clinical and Translational Sciences (UL1)UL1RR024992 · NCRR · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2007 to 2011
$45.4M
Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
ION CHANNEL REGULATION AND MODULATION IN CARDIAC MUSCLER01HL034161 · NHLBI · WASHINGTON UNIVERSITY · PI NERBONNE, JEANNE M. · 1986 to 2015
$4.6M
REPOLARIZATION AND REMODELING IN THE MAMMALIAN HEARTR01HL066388 · NHLBI · WASHINGTON UNIVERSITY · PI NERBONNE, JEANNE M. · 2000 to 2008
$2.7M
CYTOPROTECTIVE EFFECTS OF INFLAMMATION MEDIATED MEMBRANE REPAIRR01HL111094 · NHLBI · WASHINGTON UNIVERSITY · PI MANN, DOUGLAS L · 2012 to 2016
$1.9M
NCATS NIH HHS UL1 TR000448NCRR NIH HHS UL1 RR024992NHLBI NIH HHS HL-066388NHLBI NIH HHS R01 HL-034161NHLBI NIH HHS R01 HL034161NHLBI NIH HHS R01 HL066388NHLBI NIH HHS R01 HL 111094NHLBI NIH HHS R01 HL111094
6 · The paper itself

Abstract

backgroundMicroarrays have been used extensively to profile transcriptome remodeling in failing human heart, although the genomic coverage provided is limited and fails to provide a detailed picture of the myocardial transcriptome landscape. Here, we describe sequencing-based transcriptome profiling, providing comprehensive analysis of myocardial mRNA, microRNA (miRNA), and long noncoding RNA (lncRNA) expression in failing human heart before and after mechanical support with a left ventricular (LV) assist device (LVAD). METHODS AND

resultsDeep sequencing of RNA isolated from paired nonischemic (NICM; n=8) and ischemic (ICM; n=8) human failing LV samples collected before and after LVAD and from nonfailing human LV (n=8) was conducted. These analyses revealed high abundance of mRNA (37%) and lncRNA (71%) of mitochondrial origin. miRNASeq revealed 160 and 147 differentially expressed miRNAs in ICM and NICM, respectively, compared with nonfailing LV. Among these, only 2 (ICM) and 5 (NICM) miRNAs are normalized with LVAD. RNASeq detected 18 480, including 113 novel, lncRNAs in human LV. Among the 679 (ICM) and 570 (NICM) lncRNAs differentially expressed with heart failure, ≈10% are improved or normalized with LVAD. In addition, the expression signature of lncRNAs, but not miRNAs or mRNAs, distinguishes ICM from NICM. Further analysis suggests that cis-gene regulation represents a major mechanism of action of human cardiac lncRNAs.

conclusionsThe myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.

Indexed as

Gene Expression ProfilingHeart-Assist DevicesAdultAgedAged, 80 and overFemaleGene Expression RegulationHeartHeart FailureHigh-Throughput Nucleotide SequencingHumansMaleMicroRNAsMiddle AgedMyocardiumRNAMicroRNAsRNARNA, MessengerRNA, MitochondrialRNA, Untranslateddeep sequencingheart failureRNA, long noncodingventricular assist device

Identifiers

PMID24429688
PMCPMC3967509

What OpenQuestion holds

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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.