ArticleJournal of molecular and cellular cardiology2014
MAFbx/Atrogin-1 is required for atrophic remodeling of the unloaded heart.
Article in Journal of molecular and cellular cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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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.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Cardiac unloading models for myocardial reverse remodeling.Basic research in cardiology · 2026Review
- Environment-induced heat stress causes ventricular-dependent biochemical changes in the heart in female pigs.Physiological reports · 2025Article
- Effects of Left Ventricular Unloading on Cardiac Function, Heart Failure Markers, and Autophagy in Rat Hearts with Acute Myocardial Infarction.International journal of molecular sciences · 2025Article
- The role of mechanosignaling in the control of myocardial mass.American journal of physiology. Heart and circulatory physiology · 2025Review
- Targeting MuRF1 to Combat Skeletal Muscle Wasting in Cardiac Cachexia: Mechanisms and Therapeutic Prospects.Medical science monitor : international medical journal of experimental and clinical research · 2024Review
- Atrogin-1 promotes muscle homeostasis by regulating levels of endoplasmic reticulum chaperone BiP.JCI insight · 2024Article
- Regression of cardiac hypertrophy in health and disease: mechanisms and therapeutic potential.Nature reviews. Cardiology · 2023Review
- Does Myocardial Atrophy Represent Anti-Arrhythmic Phenotype?Biomedicines · 2022Review
- Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy.Life (Basel, Switzerland) · 2022Article
- TRPC Channels in Cardiac Plasticity.Cells · 2020Review
- Ubiquitin and Ubiquitin-like proteins in cardiac disease and protection.Current drug targets · 2018Review
- Post-translationally modified muscle-specific ubiquitin ligases as circulating biomarkers in experimental cancer cachexia.American journal of cancer research · 2017Article
- Atrophied cardiomyocytes and their potential for rescue and recovery of ventricular function.Heart failure reviews · 2016Review
- Myocardial energetics and the role of micronutrients in heart failure: a critical review.American journal of cardiovascular disease · 2016Review
- Rat Heterotopic Heart Transplantation Model to Investigate Unloading-Induced Myocardial Remodeling.Frontiers in cardiovascular medicine · 2016Review
- Article
- The COP9 signalosome and cullin-RING ligases in the heart.American journal of cardiovascular disease · 2015Review
- Targeting the ubiquitin-proteasome system in heart disease: the basis for new therapeutic strategies.Antioxidants & redox signaling · 2014Review
- Rethinking cardiac metabolism: metabolic cycles to refuel and rebuild the failing heart.F1000prime reports · 2014Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMechanical unloading of the failing human heart induces profound cardiac changes resulting in the reversal of a distorted structure and function. In this process, cardiomyocytes break down unneeded proteins and replace those with new ones. The specificity of protein degradation via the ubiquitin proteasome system is regulated by ubiquitin ligases. Over-expressing the ubiquitin ligase MAFbx/Atrogin-1 in the heart inhibits the development of cardiac hypertrophy, but the role of MAFbx/Atrogin-1 in the unloaded heart is not known. METHODS AND
resultsMechanical unloading, by heterotopic transplantation, decreased heart weight and cardiomyocyte cross-sectional area in wild type mouse hearts. Unexpectedly, MAFbx/Atrogin-1(-/-) hearts hypertrophied after transplantation (n=8-10). Proteasome activity and markers of autophagy were increased to the same extent in WT and MAFbx/Atrogin-1(-/-) hearts after transplantation (unloading). Calcineurin, a regulator of cardiac hypertrophy, was only upregulated in MAFbx/Atrogin-1(-/-) transplanted hearts, while the mTOR pathway was similarly activated in unloaded WT and MAFbx/Atrogin-1(-/-) hearts. MAFbx/Atrogin-1(-/-) cardiomyocytes exhibited increased calcineurin protein expression, NFAT transcriptional activity, and protein synthesis rates, while inhibition of calcineurin normalized NFAT activity and protein synthesis. Lastly, mechanical unloading of failing human hearts with a left ventricular assist device (n=18) also increased MAFbx/Atrogin-1 protein levels and expression of NFAT regulated genes.
conclusionsMAFbx/Atrogin-1 is required for atrophic remodeling of the heart. During unloading, MAFbx/Atrogin-1 represses calcineurin-induced cardiac hypertrophy. Therefore, MAFbx/Atrogin-1 not only regulates protein degradation, but also reduces protein synthesis, exerting a dual role in regulating cardiac mass.
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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.