Evidence map›Paper›PMID 40464169›Full record

ArticleJournal of cachexia, sarcopenia and muscle2025

MyoMed205 Counteracts Titin Hyperphosphorylation and the Expression of Contraction-Regulating Proteins in a Rat Model of HFpEF.

Beatrice Vahle, Antje Schauer, Antje Augstein, Maria-Elisa Prieto Jarabo, Janet Friedrich, Peggy Barthel, Anita Männel, Norman Mangner, Siegfried Labeit, T Scott Bowen and 2 more

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In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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

4 citing papers in PubMed.

  1. Review
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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

12 authors.

Beatrice VahleHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.ORCID 0009-0000-8110-1943
Antje SchauerHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.
Antje AugsteinHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.
Maria-Elisa Prieto JaraboHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.
Janet FriedrichHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.
Peggy BarthelHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.
Anita MännelHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.
Norman MangnerHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.
Siegfried LabeitDZHK Partner Site Mannheim-Heidelberg, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
T Scott BowenSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Axel LinkeHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.
Volker AdamsHeart Center, University Clinic, Department of Internal Medicine, Laboratory of Molecular and Experimental Cardiology, University of Technology Dresden, Dresden, Germany.ORCID 0000-0002-7955-7324

Funding

DZHK (German Center for Cardiovascular Research)
6 · The paper itself

Abstract

backgroundHeart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance, accompanied by alterations in the peripheral skeletal muscle (SKM). We have recently shown that titin, a giant sarcomere protein, is hyperphosphorylated in HFpEF. MuRF1 is a muscle-specific ubiquitin E3-ligase that interacts with titin. Blocking this interaction via small molecules (MyoMed205) can improve muscle function and mitochondrial activity in HFpEF. This study aimed to investigate the impact of MyoMed205 on titin phosphorylation and its association with changes in muscle structure and function.

methodsObese ZSF1 rats with established HFpEF received rat chow with (n = 15) or without (n = 15) MyoMed205 and were compared with lean littermates (n = 15), serving as controls. After 12 weeks, in vitro SKM force, atrophy and titin-as well as contractile protein expression-were evaluated (soleus and extensor digitorum longus [EDL]). Statistical analysis was performed via multiple unpaired t-test or one-way ANOVA.

resultsIn HFpEF, titin hyperphosphorylation by 13% in the EDL (p = 0.09) and 14% (p = 0.03) in the soleus muscle was evident. This hyperphosphorylation was driven in part by an increase in S11878 phosphorylation (EDL: +68%, p = 0.004; Sol: +23.8%, p = 0.03), which was linked to myofiber atrophy (r = -0.68, p = 0.006) and a decline in maximal specific muscle force (r = -0.54, p = 0.008). In the EDL, significant changes in protein expression related to atrophy (MuRF1 [+24.9%, p = 0.02], GDF8 [+20.6%, p = 0.09]) and calcium handling (slow troponin C [-46%, p = 0.02], fast troponin I [+35.8%, p = 0.02]) were found in HFpEF. All of the above-mentioned effects in HFpEF were almost completely abolished by MyoMed205 treatment, and significantly elevated titin expression was visible (+19.7%, p

conclusionsTitin hyperphosphorylation may negatively impact skeletal muscle integrity and function in HFpEF. MyoMed205 reduced titin hyperphosphorylation and was associated with preserved skeletal muscle function and mass. Further studies are necessary to confirm the direct role of titin hyperphosphorylation on muscle function and to evaluate the therapeutic potential of MyoMed205 in HFpEF.

Indexed as

ConnectinHeart FailureMuscle ContractionAnimalsDisease Models, AnimalMaleMuscle ProteinsMuscle, SkeletalPhosphorylationRatsStroke VolumeUbiquitin-Protein LigasesConnectinMuscle ProteinsTtn protein, ratUbiquitin-Protein Ligasesatrophycontractile proteinsHFpEFMuRF1MyoMed205sarcopeniaskeletal muscle functiontitinZSF1

Identifiers

PMID40464169
PMCPMC12134774

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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.