Evidence map›Paper›PMID 33301345›Full record

ArticleCirculation. Arrhythmia and electrophysiology2021

Circadian Pattern of Ion Channel Gene Expression in Failing Human Hearts.

Charles F McTiernan, Bonnie H Lemster, Kenneth C Bedi, Kenneth B Margulies, Christine S Moravec, Paishiun Nelson Hsieh, Vladimir Shusterman, Samir Saba

Open access · bronzeAbstract read
In one paragraph

Article in Circulation. Arrhythmia and electrophysiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Research Progress of BMAL1 in Heart Failure.Journal of the American Heart Association · 2025
    Review
  6. Circadian rhythms in cardiovascular disease.European heart journal · 2025
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. A new border for circadian rhythm gene NFIL3 in diverse fields of cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Review
  12. The Circadian Biology of Heart Failure.Circulation research · 2023
    Review
  13. Article
  14. Review
  15. 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

8 authors at 5 institutions in 1 country.

Charles F McTiernanHeart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (C.F.M., B.H.L., S.S.).
Bonnie H LemsterHeart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (C.F.M., B.H.L., S.S.).
Kenneth C BediDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (K.C.B).
Kenneth B MarguliesPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia (K.B.M.).
Christine S MoravecDepartment of Cardiovascular Medicine, Cleveland Clinic Foundation, OH (C.S.M.).
Paishiun Nelson HsiehSchool of Medicine, Case Western Reserve University, Cleveland, OH (P.N.H.).
Vladimir ShustermanDepartment of Internal Medicine, University of Iowa, Iowa City (V.S.).
Samir SabaHeart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (C.F.M., B.H.L., S.S.).
University of Pittsburgh · USUniversity of Pennsylvania · USCase Western Reserve University · USCleveland Clinic · USUniversity of Iowa · US

Funding

UNIVERSITY OF PITTSBURGH CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE: BPCAUL1RR024153 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2006 to 2011
$73.9M
University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Integrative genomics of human heart failureR01HL105993 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ASHLEY, EUAN A, CAPPOLA, THOMAS P. · 2011 to 2014
$8.9M
NCATS NIH HHS UL1 TR000005NCRR NIH HHS UL1 RR024153NHLBI NIH HHS R01 HL105993
6 · The paper itself

Abstract

backgroundVentricular tachyarrhythmias and sudden cardiac death show a circadian pattern of occurrence in patients with heart failure. In the rodent ventricle, a significant portion of genes, including some ion channels, shows a circadian pattern of expression. However, genes that define electrophysiological properties in failing human heart ventricles have not been examined for a circadian expression pattern.

methodsVentricular tissue samples were collected from patients at the time of cardiac transplantation. Two sets of samples (n=37 and 46, one set with a greater arrhythmic history) were selected to generate pseudo-time series according to their collection time. A third set (n=27) of samples was acquired from the nonfailing ventricles of brain-dead donors. The expression of 5 known circadian clock genes and 19 additional ion channel genes plausibly important to electrophysiological properties were analyzed by real-time polymerase chain reaction and then analyzed for the percentage of expression variation attributed to a 24-hour circadian pattern.

resultsThe 5 known circadian clock gene transcripts showed a strong circadian expression pattern. Compared with rodent hearts, the human circadian clock gene transcripts showed a similar temporal order of acrophases but with a ≈7.6 hours phase shift. Five of the ion channel genes also showed strong circadian expression. Comparable studies of circadian clock gene expression in samples recovered from nonheart failure brain-dead donors showed acrophase shifts, or weak or complete loss of circadian rhythmicity, suggesting alterations in circadian gene expression.

conclusionsVentricular tissue from failing human hearts display a circadian pattern of circadian clock gene expression but phase-shifted relative to rodent hearts. At least 5 ion channels show a circadian expression pattern in the ventricles of failing human hearts, which may underlie a circadian pattern of ventricular tachyarrhythmia/sudden cardiac death. Nonfailing hearts from brain-dead donors show marked differences in circadian clock gene expression patterns, suggesting fundamental deviations from circadian expression.

Indexed as

Circadian RhythmGene ExpressionAdultFemaleHeart FailureHumansIon ChannelsMaleMiddle AgedMyocardiumIon Channelscircadian rhythmgene expressionheart failurehumansion channels

Identifiers

PMID33301345
PMCPMC7875252
OpenAlexW3112183567

What OpenQuestion holds

Textmetadata
LicenceTDM
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.