Evidence map›Paper›PMID 39969162›Full record

ArticleEuropean heart journal2025

Cardiac dysfunction related to cardiac mRNA and protein traffic impairment due to reduced unconventional motor protein myosin-5b expression.

Maren Heimerl, Sergej Erschow, Mirco Müller-Olling, Dietmar J Manstein, Niels Decher, Silke Kauferstein, Tina Jenewein, Andreas Pich, Melanie Ricke-Hoch, Denise Hilfiker-Kleiner

Abstract read
In one paragraph

Article in European heart journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Maren HeimerlDepartment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany.
Sergej ErschowDepartment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany.
Mirco Müller-OllingDepartment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany.
Dietmar J MansteinInstitute for Biophysical Chemistry, Hannover Medical School, Fritz Hartmann Centre for Medical Research, Carl-Neuberg Str. 1, Hannover 30625, Germany.ORCID 0000-0003-0763-0147
Niels DecherDepartment of Vegetative Physiology and Center for Mind, Brain and Behavior (CMBB), Medical Faculty, Philipps University Marburg, Deutschausstrasse 1-2, Marburg 35037, Germany.ORCID 0000-0002-9433-687X
Silke KaufersteinInstitute of Legal Medicine, Goethe University Frankfurt, University Hospital, Kennedyallee 104, Frankfurt am Main 60598, Germany.ORCID 0000-0003-0066-8679
Tina JeneweinInstitute of Legal Medicine, Goethe University Frankfurt, University Hospital, Kennedyallee 104, Frankfurt am Main 60598, Germany.
Andreas PichCore Facility Proteomics, Institute of Toxicology, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany.ORCID 0000-0001-8444-0940
Melanie Ricke-HochDepartment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany.ORCID 0000-0001-5479-2275
Denise Hilfiker-KleinerDepartment of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany.ORCID 0000-0001-6065-9649

Funding

Clinical Research Group HI 842/10-1Clinical Research Group HI 842/10-2Clinical Research Group KFO 311Clinical Research Group RI 2531/2-1 and RI 2531/2-2Deutsche ForschungsgemeinschaftDFGDFG DE1482-9/1European Joint Project on Rare Diseases ConsortiumFoundation Leducq 19CVD02German Federal Ministry of EducationREBIRTH I/IIResearch Grant Agreement 01GM1922B
6 · The paper itself

Abstract

BACKGROUND AND

aimsThe present study analysed the expression patterns of class-5 myosin motor proteins (MYO5a, b, and c) in the heart with a specific focus on the role of MYO5b.

methodsRNA-sequencing, quantitative real-time polymerase chain reaction, immunohistochemistry, Western blot, immunoprecipitation, and proteomics were performed in mice and human tissues. Functional analyses were performed in mice with a cardiac-specific knockout (KO) of MYO5b (αMHC-Cretg/-; MYO5bflox/flox), wild-type (WT) (MYO5bflox/flox), and αMHC-Cretg/- mice and in isolated adult cardiomyocytes. Next-generation sequencing screened for MYO5B gene variants in a cohort of sudden cardiac death in the young/sudden infant death syndrome patients.

resultsThe expression of MYO5b, but not MYO5a or c, increased during postnatal cardiomyocyte maturation. Myosin-5b was reduced in end-stage failing human hearts and infarcted murine hearts. Heterozygous rare and likely pathogenic missense MYO5B gene variants (n = 6) were identified in three patients of a cohort of young patients (n = 95) who died of sudden cardiac death in the young/sudden infant death syndrome. MYO5b-KO mice revealed impaired electric conductance and metabolism, developed sarcomeric disarrangement, heart failure and death with altered mRNA levels for genes involved in sarcomere organization, fatty acid and glucose metabolism, ion channel sub-units, and Ca2+-homeostasis prior to heart failure. In cardiomyocytes, myosin-5b is associated with mitochondrial and ribosomal proteins. Myosin-5b-associated ribonucleoprotein particles (RNPs) contained mRNAs of sarcomeric, metabolic, cytoskeletal, and ion channel proteins.

conclusionsMYO5b is the major MYO5 gene expressed in postnatal cardiomyocytes where it transports vesicles, proteins, and multi-protein complexes. Among these are mRNA/RNP complexes affecting electric conductance, sarcomere homeostasis, cell metabolism, and cytoskeletal organization. Impairment in MYO5b expression and function promotes cardiac dysfunction, heart failure, and death.

Indexed as

Myosin Heavy ChainsMyosin Type VRNA, MessengerAdultAnimalsDeath, Sudden, CardiacFemaleHeart FailureHumansMaleMiceMice, KnockoutMyocytes, CardiacMyosin Heavy ChainsMyosin Type VRNA, MessengerArrhythmiasClass-5 myosin motor proteins MYO5a and MYO5bHeart failureRibosomesRNA traffickingSarcomere

Identifiers

PMID39969162
PMCPMC12208777

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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.