Evidence map›Paper›PMID 30102883›Full record

ArticleJournal of molecular and cellular cardiology2018

Cardiac-specific knockout of Lmod2 results in a severe reduction in myofilament force production and rapid cardiac failure.

Christopher T Pappas, Gerrie P Farman, Rachel M Mayfield, John P Konhilas, Carol C Gregorio

Abstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

30 citing papers in PubMed, 37 citations in OpenAlex.

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  12. Developmental nicotine exposure alters cardiovascular structure and function in neonatal and juvenile rats.American journal of physiology. Heart and circulatory physiology · 2024
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  18. A nemaline myopathy-linked mutation inhibits the actin-regulatory functions of tropomodulin and leiomodin.Proceedings of the National Academy of Sciences of the United States of America · 2023
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  19. Article
  20. LMOD2-related dilated cardiomyopathy presenting in late infancy.American journal of medical genetics. Part A · 2022
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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

5 authors at 1 institution in 1 country.

Christopher T PappasDepartment of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA; Department of Physiology and Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA. Electronic address: ctpappas@email.arizona.edu.
Gerrie P FarmanDepartment of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA; Department of Physiology and Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Rachel M MayfieldDepartment of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA; Department of Physiology and Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
John P KonhilasDepartment of Physiology and Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Carol C GregorioDepartment of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA; Department of Physiology and Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
University of Arizona · US

Funding

Deciphering the role of Lmod2 in thin filament length regulation and dilated cardiomyopathyR01HL123078 · NHLBI · UNIVERSITY OF ARIZONA · PI Carol C Gregorio, Shashank Shekhar · 2015 to 2026
$5.6M
NHLBI NIH HHS R01 HL123078
6 · The paper itself

Abstract

Leiomodin-2 (Lmod2) is a striated muscle-specific actin binding protein that is implicated in assembly of thin filaments. The necessity of Lmod2 in the adult mouse and role it plays in the mechanics of contraction are unknown. To answer these questions, we generated cardiac-specific conditional Lmod2 knockout mice (cKO). These mice die within a week of induction of the knockout with severe left ventricular systolic dysfunction and little change in cardiac morphology. Cardiac trabeculae isolated from cKO mice have a significant decrease in maximum force production and a blunting of myofilament length-dependent activation. Thin filaments are non-uniform and substantially reduced in length in cKO hearts, affecting the functional overlap of the thick and thin filaments. Remarkably, we also found that Lmod2 levels are directly linked to thin filament length and cardiac function in vivo, with a low amount (<20%) of Lmod2 necessary to maintain cardiac function. Thus, Lmod2 plays an essential role in maintaining proper cardiac thin filament length in adult mice, which in turn is necessary for proper generation of contractile force. Dysregulation of thin filament length in the absence of Lmod2 contributes to heart failure.

Indexed as

Analysis of VarianceAnimalsCalciumCytoskeletal ProteinsEchocardiographyGene Knockout TechniquesHeart FailureLinear ModelsMiceMice, Inbred C57BLMice, KnockoutMuscle ContractionMuscle ProteinsMyocytes, CardiacMyofibrilsSarcomeresCalciumCytoskeletal Proteinsleiomodin protein, mouseMuscle ProteinsActin-thin filamentsCardiomyopathySarcomere

Identifiers

PMID30102883
PMCPMC6324932
OpenAlexW2886489204

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.