Evidence map›Paper›PMID 35114812›Full record

ArticleCirculation2022

lncExACT1 and DCHS2 Regulate Physiological and Pathological Cardiac Growth.

Haobo Li, Lena E Trager, Xiaojun Liu, Margaret H Hastings, Chunyang Xiao, Justin Guerra, Samantha To, Guoping Li, Ashish Yeri, Rodosthenis Rodosthenous and 6 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
10.1field-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.

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

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
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  5. Article
  6. Long non-coding RNAs in exercise: the hidden regulators of adaptation.Pflugers Archiv : European journal of physiology · 2026
    Review
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  17. Article
  18. Cardiac fibrosis: from mechanisms and models to medicines.Trends in pharmacological sciences · 2025
    Review
  19. Review
  20. Article

22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Haobo LiCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).ORCID 0000-0002-5660-7835
Lena E TragerCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Xiaojun LiuCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Margaret H HastingsCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Chunyang XiaoCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Justin GuerraCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).ORCID 0000-0001-8507-5922
Samantha ToCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Guoping LiCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Ashish YeriCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Rodosthenis RodosthenousCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Michael G SilvermanCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).ORCID 0000-0002-5885-1866
Saumya DasCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).ORCID 0000-0002-4521-4606
Amrut V AmbardekarDivision of Cardiology, University of Colorado Anschutz Medical Campus, Aurora (A.V.A., M.R.B.).ORCID 0000-0003-3503-4203
Michael R BristowDivision of Cardiology, University of Colorado Anschutz Medical Campus, Aurora (A.V.A., M.R.B.).ORCID 0000-0002-8860-4698
Juan Manuel González-RosaCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Anthony RosenzweigCorrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).ORCID 0000-0001-6387-0386
Harvard University · USUniversity of Colorado Anschutz Medical Campus · US

Funding

NIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1M
Understanding the Cardiac Benefits of Exercise at the Cellular and Molecular LevelR35HL155318 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANTHONY ROSENZWEIG · 2021 to 2026
$5.4M
Role of Activin Type II receptor signaling in age-related heart failureR01AG061034 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSENZWEIG, ANTHONY · 2019 to 2023
$3.0M
NCATS NIH HHS UL1 TR002535NHLBI NIH HHS R35 HL155318NIA NIH HHS R01 AG061034
6 · The paper itself

Abstract

backgroundThe heart grows in response to pathological and physiological stimuli. The former often precedes cardiomyocyte loss and heart failure; the latter paradoxically protects the heart and enhances cardiomyogenesis. The mechanisms underlying these differences remain incompletely understood. Although long noncoding RNAs (lncRNAs) are important in cardiac development and disease, less is known about their roles in physiological hypertrophy or cardiomyogenesis.

methodsRNA sequencing was applied to hearts from mice after 8 weeks of voluntary exercise-induced physiological hypertrophy and cardiomyogenesis or transverse aortic constriction for 2 or 8 weeks to induce pathological hypertrophy or heart failure. The top lncRNA candidate was overexpressed in hearts with adeno-associated virus vectors and inhibited with antisense locked nucleic acid-GapmeRs to examine its function. Downstream effectors were identified through promoter analyses and binding assays. The functional roles of a novel downstream effector, dachsous cadherin-related 2 (DCHS2), were examined through transgenic overexpression in zebrafish and cardiac-specific deletion in Cas9-knockin mice.

resultsWe identified exercise-regulated cardiac lncRNAs, called lncExACTs. lncExACT1 was evolutionarily conserved and decreased in exercised hearts but increased in human and experimental heart failure. Cardiac lncExACT1 overexpression caused pathological hypertrophy and heart failure; lncExACT1 inhibition induced physiological hypertrophy and cardiomyogenesis, protecting against cardiac fibrosis and dysfunction. lncExACT1 functioned by regulating microRNA-222, calcineurin signaling, and Hippo/Yap1 signaling through DCHS2. Cardiomyocyte DCHS2 overexpression in zebrafish induced pathological hypertrophy and impaired cardiac regeneration, promoting scarring after injury. In contrast, murine DCHS2 deletion induced physiological hypertrophy and promoted cardiomyogenesis.

conclusionsThese studies identify lncExACT1-DCHS2 as a novel pathway regulating cardiac hypertrophy and cardiomyogenesis. lncExACT1-DCHS2 acts as a master switch toggling the heart between physiological and pathological growth to determine functional outcomes, providing a potentially tractable therapeutic target for harnessing the beneficial effects of exercise.

Indexed as

Heart FailureMicroRNAsRNA, Long NoncodingAnimalsCadherin Related ProteinsCardiomegalyDisease Models, AnimalHumansMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacZebrafishCadherin Related ProteinsMicroRNAsMIR222, humanRNA, Long Noncodingexerciseheart failureHippo signaling pathwayhypertrophyRNA, long noncodingYap1 protein, human

Identifiers

PMID35114812
PMCPMC9056949
OpenAlexW4210780578

What OpenQuestion holds

Textmetadata
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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.