ArticleCardiovascular research2014
Desmin modifications associate with amyloid-like oligomers deposition in heart failure.
Article in Cardiovascular research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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.
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.
Who cites it
52 citing papers in PubMed, 83 citations in OpenAlex.
- Failure of efficient cardiac proteostatic adaptations to chronic cAMP-stress is associated with accelerated heart aging.GeroScience · 2026Article
- Chaperone proteins protect against desmin fragment amyloid aggregation.Biophysical journal · 2026Article
- Misfolded Proteins and Cognitive Decline: Mechanistic Insights into Neurodegenerative Disorders.Neurology international · 2026Review
- Phosphorylation of CRYAB induces a condensatopathy to worsen post-myocardial infarction left ventricular remodeling.The Journal of clinical investigation · 2025Article
- Article
- Thioflavin T in-gel staining forFrontiers in molecular biosciences · 2025Article
- Acute resistance exercise and training reduce desmin phosphorylation at serine 31 in human skeletal muscle, making the protein less prone to cleavage.Scientific reports · 2024Article
- Review
- Article
- Considering impact of age and sex on cardiac cytoskeletal components.American journal of physiology. Heart and circulatory physiology · 2024Review
- Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation.Stem cell research & therapy · 2024Article
- The microtubule signature in cardiac disease: etiology, disease stage, and age dependency.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2023Article
- Desmin Reorganization by Stimuli Inducing Oxidative Stress and Electrophiles: Role of Its Single Cysteine Residue.Antioxidants (Basel, Switzerland) · 2023Article
- The AAA-ATPase ATAD1 and its partners promote degradation of desmin intermediate filaments in muscle.EMBO reports · 2022Article
- Extracellular stiffness induces contractile dysfunction in adult cardiomyocytes via cell-autonomous and microtubule-dependent mechanisms.Basic research in cardiology · 2022Article
- Global O-GlcNAcylation changes impact desmin phosphorylation and its partition toward cytoskeleton in C2C12 skeletal muscle cells differentiated into myotubes.Scientific reports · 2022Article
- Mechanistic implications of altered protein expression in rheumatic heart disease.Heart failure reviews · 2022Review
- Keratin 19 interacts with GSK3β to regulate its nuclear accumulation and degradation of cyclin D3.Molecular biology of the cell · 2021Article
- Gain-of-function mutation in ubiquitin-ligase KLHL24 causes desmin degradation and dilatation in hiPSC-derived engineered heart tissues.The Journal of clinical investigation · 2021Article
- Desmin aggrephagy in rat and human ischemic heart failure through PKCζ and GSK3β as upstream signaling pathways.Cell death discovery · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsThe ultimate cause of heart failure (HF) is not known to date. The cytoskeletal protein desmin is differentially modified and forms amyloid-like oligomers in HF. We postulated that desmin post-translational modifications (PTMs) could drive aberrant desmin aggregation in HF. Therefore, we identified these PTMs and investigated their impact on desmin amyloidogenicity in human and experimental HF. METHODS AND
resultsWe detected increased levels of selectively phosphorylated and cleaved desmin in a canine pacing model of dyssynchronous HF (DHF) compared with either controls or animals treated with cardiac resynchronization therapy (CRT). This unique animal model combines clinically relevant features with the possibility of a partly rescued phenotype. We confirmed analogous changes in desmin modifications in human HF and identified two phosphorylation sites within a glycogen synthase kinase 3 (GSK3) consensus sequence. Desmin-positive oligomers were also increased in DHF hearts compared with controls. Their amyloid properties were decreased by treatment with CRT or an anti-amyloid small molecule. Finally, we confirmed GSK3's involvement with desmin phosphorylation using an in vitro model.
conclusionsBased on these findings, we postulate a new mechanism of cardiac toxicity based on the PTM-driven accumulation of desmin amyloid-like oligomers. Phosphorylation and cleavage as well as oligomers formation are reduced by treatment (CRT) indicating a relationship between the three. Finally, the decrease of desmin amyloid-like oligomers with CRT or small molecules points both to a general mechanism of HF based on desmin toxicity that is independent of protein mutations and to novel potential therapies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.