ArticleFrontiers in physiology2014
Proteasome inhibition slightly improves cardiac function in mice with hypertrophic cardiomyopathy.
Article in Frontiers in physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- UBA1 promotes cardiac hypertrophy by suppressing autophagy via targeting ATG5 for ubiquitination.Cell communication and signaling : CCS · 2026Article
- Experimental Models of Hypertrophic Cardiomyopathy: A Systematic Review.JACC. Basic to translational science · 2025Review
- Sacubitril/valsartan reduces proteasome activation and cardiomyocyte area in an experimental mouse model of hypertrophy.Journal of molecular and cellular cardiology plus · 2024Article
- Cardiovascular Toxicity of Proteasome Inhibitors: Underlying Mechanisms and Management Strategies:JACC. CardioOncology · 2023Review
- Titin (TTN): from molecule to modifications, mechanics, and medical significance.Cardiovascular research · 2022Review
- Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.International journal of molecular sciences · 2022Review
- A high-throughput screening identifies ZNF418 as a novel regulator of the ubiquitin-proteasome system and autophagy-lysosomal pathway.Autophagy · 2021Article
- Genetic, clinical, molecular, and pathogenic aspects of the South Asian-specific polymorphic MYBPC3Biophysical reviews · 2020Review
- Altered C10 domain in cardiac myosin binding protein-C results in hypertrophic cardiomyopathy.Cardiovascular research · 2019Article
- Genome-Wide RNAi Screen Identifies Regulators of Cardiomyocyte Necrosis.ACS pharmacology & translational science · 2019Article
- A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay.Circulation · 2019Article
- Emergence of Members of TRAF and DUB of Ubiquitin Proteasome System in the Regulation of Hypertrophic Cardiomyopathy.Frontiers in genetics · 2018Review
- Nebivolol Desensitizes Myofilaments of a Hypertrophic Cardiomyopathy Mouse Model.Frontiers in physiology · 2017Article
- Proteasome inhibitors attenuated cholesterol-induced cardiac hypertrophy in H9c2 cells.BMB reports · 2016Article
- Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype.Frontiers in physiology · 2016Review
- Epigallocatechin-3-Gallate Accelerates Relaxation and CaFrontiers in physiology · 2016Article
- Ongoing controversies surrounding cardiac remodeling: is it black and white-or rather fifty shades of gray?Frontiers in physiology · 2015Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A growing line of evidence indicates a dysfunctional ubiquitin-proteasome system (UPS) in cardiac diseases. Anti-hypertrophic effects and improved cardiac function have been reported after treatment with proteasome inhibitors in experimental models of cardiac hypertrophy. Here we tested whether proteasome inhibition could also reverse the disease phenotype in a genetically-modified mouse model of hypertrophic cardiomyopathy (HCM), which carries a mutation in Mybpc3, encoding the myofilament protein cardiac myosin-binding protein C. At 7 weeks of age, homozygous mutant mice (KI) have 39% higher left ventricular mass-to-body-weight ratio and 29% lower fractional area shortening (FAS) than wild-type (WT) mice. Both groups were treated with epoxomicin (0.5 mg/kg/day) or vehicle for 1 week via osmotic minipumps. Epoxomicin inhibited the chymotrypsin-like activity by ~50% in both groups. All parameters of cardiac hypertrophy (including the fetal gene program) were not affected by epoxomicin treatment in both groups. In contrast, FAS was 12% and 35% higher in epoxomicin-treated than vehicle-treated WT and KI mice, respectively. To identify which genes or pathways could be involved in this positive effect, we performed a transcriptome analysis in KI and WT neonatal cardiac myocytes, treated or not with the proteasome inhibitor MG132 (1 μM, 24 h). This revealed 103 genes (four-fold difference; 5% FDR) which are commonly regulated in both KI and WT cardiac myocytes. Thus, even in genetically-modified mice with manifest HCM, proteasome inhibition showed beneficial effects, at least with regard to cardiac function. Targeting the UPS in cardiac diseases remains therefore a therapeutic option.
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