Myostatin activation in patients with advanced heart failure and after mechanical unloading
Open accessAbstract
AIMS: Myostatin inhibits myoblast differentiation/proliferation and may play a role in heart failure (HF) and reverse remodelling after left ventricular assist device (LVAD) support. This study sought to characterize myostatin expression and activation in advanced HF before and after LVAD support. METHODS AND RESULTS: Left ventricular tissue pairs were collected at LVAD implantation (core) and at cardiac transplantation/LVAD explantation in patients with advanced ischaemic (ICM-ischaemic cardiomyopathy) and non-ischaemic (DCM-dilated cardiomyopathy) HF. Normal cardiac tissue (control) was obtained from hearts not placed for transplantation. Serum was collected independently from patients with stable DCM HF and from healthy controls. Full-length and cleaved propeptide myostatin levels were quantified by western blot analysis. Dilated cardiomyopathy propeptide levels at core were significantly higher than control and significantly increased after LVAD support. Ischaemic cardiomyopathy propeptide levels were higher than control, but did not change after LVAD support. No changes in full-length levels were seen. Serum myostatin levels were significantly higher in DCM HF patients than in healthy controls. CONCLUSION: This is the first clinical evidence that myostatin activation is increased in HF. Myostatin may affect cardiac hypertrophy and may mediate regression of cellular hypertrophy after mechanical unloading.
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Patients with heart failure and cancer present increased serum levels of myostatin, which can result in cachexia.
“The importance of myostatin as an atrophic component is highlighted in patients with HF and cancer, who present increased serum levels of this protein, which can result in cachexia, which can only be reversed by the deletion of the gene, as can be observed in in vitro assays and transgenic animal models (George et al., 2010; Heineke et al., 2010).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as George et al., 2010
The Results report higher serum myostatin in patients with dilated-cardiomyopathy heart failure than in healthy controls. The Discussion says circulating myostatin may contribute to cardiac cachexia, but the study found no relationship with BMI or exercise capacity and did not study cancer patients. The cancer portion of the claim is therefore unsupported by this paper. (LLM, conf=0.88)
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“The importance ofmyostatin as an atrophic component is highlighted in patients with HF and cancer, who present increased serum levels of this protein, which can result in cachexia, which can only be reversed by the deletion of the gene, as can be observed in in vitro assays and transgenic animal models (George et al.,…”
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- Authors
- George, I., Bish, L. T., Kamalakkannan, G., Petrilli, C. M., Oz, M. C., Naka, Y., Lee Sweeney, H., & Maybaum, S.
- Affiliations
- Columbia University Irving Medical Center (US)
- University of Pennsylvania (US)
- Albert Einstein College of Medicine (US)
- Department of Physiology, University of Pennsylvania , Philadelphia, PA ,
- Corresponding author
- George, Isaac
- Venue
- European Journal of Heart Failure
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-04-21
- Volume
- 12
- Issue
- 5
- Pages
- 444-453
- ISSN
- 1388-9842 (ISSN-L)
- 1879-0844
- PMC
- PMC2857990
- OpenAlex
- W2074161753
- Cited by
- 136
- References
- 34
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 4 · 2022: 15 · 2021: 6 · 2020: 6 · 2019: 9 · 2018: 6 · 2017: 12 · 2016: 8 · 2015: 10 · 2014: 10 · 2013: 8 · 2012: 13
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Heart Failure (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL007748, T32-HL-07854, T32HL007854)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR052646)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Mechanical Circulatory Support Devices
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- myostatin, advanced heart failure, left ventricular assist device, mechanical unloading, myostatin propeptide, ischemic cardiomyopathy, dilated cardiomyopathy, cardiac hypertrophy, reverse remodeling, left ventricular tissue
- MeSH terms
- Adult, Analysis of Variance, Cardiomyopathy, Dilated, Female, Heart Failure, Heart-Assist Devices, Humans, Male, Middle Aged, Phosphorylation, Prospective Studies, Pulmonary Wedge Pressure, Time Factors, Blotting, Western, Linear Models, Case-Control Studies, Transforming Growth Factor beta, Myocardial Ischemia, Disease Progression, Muscle, Skeletal, Myoblasts, Cell Proliferation, Bone Morphogenetic Protein 1, Myostatin
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