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Genetic Deletion of Myostatin From the Heart Prevents Skeletal Muscle Atrophy in Heart Failure
Open accessAbstract
BACKGROUND: Cardiac cachexia is characterized by an exaggerated loss of skeletal muscle, weakness, and exercise intolerance, although the cause of these effects remains unknown. Here, we hypothesized that the heart functions as an endocrine organ in promoting systemic cachexia by secreting peptide factors such as myostatin. Myostatin is a cytokine of the transforming growth factor-beta superfamily that is known to control muscle wasting. METHODS AND RESULTS: We used a Cre/loxP system to ablate myostatin (Mstn gene) expression in a cell type-specific manner. As expected, elimination of Mstn selectively in skeletal muscle with a myosin light chain 1f (MLC1f)-cre allele induced robust hypertrophy in all skeletal muscle. However, heart-specific deletion of Mstn with an Nkx2.5-cre allele did not alter baseline heart size or secondarily affect skeletal muscle size, but the characteristic wasting and atrophy of skeletal muscle that typify heart failure were not observed in these heart-specific null mice, indicating that myocardial myostatin expression controls muscle atrophy in heart failure. Indeed, myostatin levels in the plasma were significantly increased in wild-type mice subjected to pressure overload-induced cardiac hypertrophy but not in Mstn heart-specific deleted mice. Moreover, cardiac-specific overexpression of myostatin, which increased circulating levels of myostatin by 3- to 4-fold, caused a reduction in weight of the quadriceps, gastrocnemius, soleus, and even the heart itself. Finally, to investigate myostatin as a potential therapeutic target for the treatment of muscle wasting in heart failure, we infused a myostatin blocking antibody (JA-16), which promoted greater maintenance of muscle mass in heart failure. CONCLUSIONS: Myostatin released from cardiomyocytes induces skeletal muscle wasting in heart failure. Targeted inhibition of myostatin in cardiac cachexia might be a therapeutic option in the future.
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“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 Heineke et al., 2010
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Cites
Regulation of skeletal muscle mass in mice by a new TGF-p superfamily member
McPherron, A. C., Lawler, A. M., & Lee, S.-J. (1997) · Nature · doi:10.1038/387083a0 · Cited by 4,013
Heart Disease and Stroke Statistics—2008 Update
Writing Group Members, Rosamond, W. D., Flegal, K. M., Furie, K. L., Go, A. S., Greenlund, K. J., Haase, N., Hailpern, S. M., Ho, M., Howard, V. J., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.187998 · Cited by 3,799
Wasting as independent risk factor for mortality in chronic heart failure
Anker, S. D., Ponikowski, P. P., Varney, S. J., Chua, T. P., Clark, A. L., Webb-Peploe, K., Harrington, D., Kox, W. J., Poole-Wilson, P. A., & Coats, A. J. S. (1997) · The Lancet · doi:10.1016/s0140-6736(96)07015-8 · Cited by 1,399
Induction of Cachexia in Mice by Systemically Administered Myostatin
Zimmers, T. A., Davies, M. V., Koniaris, L. G., Haynes, P. A., Esquela‐Kerscher, A., Tomkinson, K. N., McPherron, A. C., Wolfman, N. M., & Lee, S. (2002) · Science · doi:10.1126/science.1069525 · Cited by 908
Functional improvement of dystrophic muscle by myostatin blockade
Bogdanovich, S., Krag, T. O. B., Barton, E. R., Morris, L. D., Whittemore, L.-A., Ahima, R. S., & Khurana, T. S. (2002) · Nature · doi:10.1038/nature01154 · Cited by 831
REGULATION OF MUSCLE MASS BY MYOSTATIN
Lee, S.-J. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.012103.135836 · Cited by 819
Calcineurin/NFAT Coupling Participates in Pathological, but not Physiological, Cardiac Hypertrophy
Wilkins, B. J., Dai, Y., Bueno, O. F., Parsons, S. A., Xu, J., Plank, D. M., Jones, F. S., Kimball, T. R., & Molkentin, J. D. (2003) · Circulation Research · doi:10.1161/01.res.0000109415.17511.18 · Cited by 762
MANCINI, D. M., Walter, G., Reichek, N., Lenkinski, R. E., McCully, K. K., Mullen, J. L., & Wilson, J. R. (1992) · Circulation · doi:10.1161/01.cir.85.4.1364 · Cited by 736
Anker, S. D., Negassa, A., Coats, A. J. S., Afzal, R., Poole-Wilson, P. A., Cohn, J. N., & Yusuf, S. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12892-9 · Cited by 734
Abnormalities of skeletal muscle in patients with chronic heart failure
Lipkin, D. P., Jones, D. A., Round, J. M., & Poole-Wilson, P. A. (1988) · International Journal of Cardiology · doi:10.1016/0167-5273(88)90164-7 · Cited by 374
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Items 101–200 of 238
Hoogaars, W. M. H., & Jaspers, R. T. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1435-3_8 · Cited by 44
Stanciu, A. E. (2019) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.002 · Cited by 42
Establishment and phenotypic analysis of an Mstn knockout rat
Gu, H., Cao, Y., Qiu, B., Zhou, Z., Deng, R., Chen, Z., Li, R., Li, X., Wei, Q., Xia, X., et al. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.06.030 · Cited by 40
Cancer—A Major Cardiac Comorbidity With Implications on Cardiovascular Metabolism
Finke, D., Heckmann, M. B., Frey, N., & Lehmann, L. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.729713 · Cited by 40
Paracrine and endocrine modes of myostatin action
Lee, Y., Huynh, T. V., & Lee, S. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00874.2015 · Cited by 40
“In particular, systemic overexpression of myostatin has been shown to induce profound muscle loss (26), and increased MSTN levels in serum have been observed in disease states such as cancer, acquired immunodeficiency syndrome, chronic kidney failure, and heart failure (5, 8, 9, 22).”
BackgroundMicroRNAs, heart failure, and aging: potential interactions with skeletal muscle
Murach, K. A., & McCarthy, J. J. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9572-5 · Cited by 38
“Other compounds such as myostatin released from cardiac tissue during heart failure can strongly regulate skeletal muscle mass [52].”
Castillero, E., Akashi, H., Najjar, M., Ji, R., Brandstetter, L. M., Wang, C. K., Liao, X., Zhang, X., Sperry, A., Gailes, M., et al. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00302.2019 · Cited by 35
Proteomic profiling of muscle fibre type shifting in neuromuscular diseases
Dowling, P., Murphy, S., & Ohlendieck, K. (2016) · Expert Review of Proteomics · doi:10.1080/14789450.2016.1209416 · Cited by 37
“Myostatin released from cardiomyocytes was found to have more pronounced tissue-wasting effects in slow soleus muscle as compared to faster twitching quadriceps and gastrocnemius muscles when examining cardiac cachexia [71].”
BackgroundRNA-seq reveals transcriptome changes in goats following myostatin gene knockout
Wang, L., Cai, B., Zhou, S., Zhu, H., Qu, L., Wang, X., & Chen, Y. (2017) · PLoS ONE · doi:10.1371/journal.pone.0187966 · Cited by 35
Predictive value of serum myostatin for the severity and clinical outcome of heart failure
Chen, P., Liu, Z., Luo, Y., Chen, L., Li, S., Pan, Y., Lei, X., Wu, D., & Xu, D. (2019) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2019.04.017 · Cited by 36
Cardiac‐Secreted Factors as Peripheral Metabolic Regulators and Potential Disease Biomarkers
Dewey, C. M., Spitler, K. M., Ponce, J., Hall, D. D., & Grueter, C. E. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.115.003101 · Cited by 40
“The authors concluded the antibody intervention was not as effective as a genetic deletion (Mstn / ) model of myostatin; interestingly, Mstn / mice lacked myostatin before TAC.(141) These results suggest earlier inhibition of myostatin for optimal therapy.”
BackgroundInfluentialResearch on cachexia, sarcopenia and skeletal muscle in cardiology
Coats, A. J. S. (2012) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1007/s13539-012-0090-6 · Cited by 35
“Myostatin [59], a powerful inhibitor of skeletal muscle growth, is the subject of strategies to inhibit its activity and promote muscle growth [60–62].”
Cardiokines as Modulators of Stress-Induced Cardiac Disorders
Planavila, A., Fernández‐Solà, J., & Villarroya, F. (2017) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2017.01.002 · Cited by 38
Chiba, A., Watanabe‐Takano, H., Miyazaki, T., & Mochizuki, N. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2723-6 · Cited by 37
Zhao, J., & Pei, L. (2020) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2020.05.007 · Cited by 36
“Myostatin (GDF-8) Reducing skeletal muscle mass HF, AMI, cardiac cachexia (50,52,76,77)”
BackgroundBreitbart, A., Scharf, G. M., Duncker, D., Widera, C., Gottlieb, J., Vogel, A., Schmidt, S., Brandes, G., Heuft, H., Lichtinghagen, R., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080454 · Cited by 34
“Increased serum levels of the myostatin ligand were found to accompany enhanced tissue expression in mice with heart failure, but it is not known whether this is also the case in patients [6].”
BackgroundResultInfluentialTakada, S., Sabe, H., & Kinugawa, S. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00079 · Cited by 34
Effect of Exercise on Secondary Sarcopenia: A Comprehensive Literature Review
Supriya, R., Singh, K. P., Gao, Y., Gu, Y., & Baker, J. S. (2021) · Biology · doi:10.3390/biology11010051 · Cited by 34
“Further evidence that myostatin modulates muscle size is provided by observations that animals lacking the gene [102] and humans with mutations in both copies of the gene [103] have greater muscle mass.”
BackgroundSkeletal Muscle Changes in Chronic Cardiac Disease and Failure
Kennel, P. J., MANCINI, D. M., & Schulze, P. C. (2015) · Comprehensive physiology · doi:10.1002/cphy.c110003 · Cited by 36
Yanagisawa, S., Inden, Y., Yoshida, N., Kato, H., Miyoshi-Fujii, A., Mizutani, Y., Ito, T., Kamikubo, Y., Kanzaki, Y., Hirai, M., et al. (2015) · Heart and Vessels · doi:10.1007/s00380-015-0765-y · Cited by 32
Myostatin signaling is up-regulated in female patients with advanced heart failure
Ishida, J., Konishi, M., Saitoh, M., Anker, M. S., Anker, S. D., & Springer, J. (2017) · International Journal of Cardiology · doi:10.1016/j.ijcard.2017.03.153 · Cited by 31
“Interestingly, heart-specific deletion of myostatin attenuated skeletal muscle atrophy in an animal model of HF, indicating that increased myostatin signaling was associated with muscle wasting in HF [9].”
BackgroundHeart over mind: metabolic control of white adipose tissue and liver
Nakamura, M., & Sadoshima, J. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201404749 · Cited by 30
“…(known to be a cardiokine) in the heart (Callis et al , 2009; Shimano et al , 2012), which in turn induces cachexia, characterized by body and muscle wasting (Anker et al , 1997; Lee, 2004; Heineke et al , 2010), and increases mortality in patients with heart failure (George et al , 2010).”
Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia
Elkina, Y., Palus, S., Tschirner, A., Hartmann, K., von Haehling, S., Doehner, W., Mayer, U., Coats, A. J. S., Beadle, J. W., Anker, S. D., et al. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.10.022 · Cited by 29
Revisiting skeletal myopathy and exercise training in heart failure: Emerging role of myokines
Ramírez‐Vélez, R., González, A., García‐Hermoso, A., Latasa, I., Izquierdo, M., & Dı́ez, J. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155348 · Cited by 32
Plasma myostatin measured by a competitive ELISA using a highly specific antiserum
Wintgens, K. F., Dschietzig, T. B., Stoeva, S., Paulsson, M., & Armbruster, F. P. (2012) · Clinica Chimica Acta · doi:10.1016/j.cca.2012.04.023 · Cited by 29
“32 [25–41] ng/ml).”
BackgroundMethodSkeletal muscle protein metabolism in human heart failure
Callahan, D. M., & Toth, M. J. (2012) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32835a8842 · Cited by 27
Tourki, B., & Halade, G. V. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.695952 · Cited by 31
“This latter has been connected to the release of myostatin by the atrophic heart muscle, which induces muscle wasting in HF (12).”
BackgroundMoreira‐Gonçalves, D., Padrão, A. I., Ferreira, R. M., Justino, J., Nogueira‐Ferreira, R., Neuparth, M. J., Vitorino, R. M. P., Fonseca, H., Silva, A. F., Duarte, J. A., et al. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.10.002 · Cited by 27
Omics/systems biology and cancer cachexia
Gallagher, I. J., Jacobi, C., Tardif, N., Rooyackers, O., & Fearon, K. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.12.022 · Cited by 28
Méloux, A., Rochette, L., Maza, M., Bichât, F., Tribouillard, L., Cottin, Y., Zeller, M., & Vergely, C. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm9010116 · Cited by 27
“Consequently, it has been suggested that the heart could function as an endocrine organ promoting skeletal or myocardial muscle wasting, inducing cardiac muscle weakness [25].”
BackgroundTakada, S., Sabe, H., & Kinugawa, S. (2021) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00100.2021 · Cited by 29
Inflammageing and Cardiovascular System: Focus on Cardiokines and Cardiac-Specific Biomarkers
Perrone, M. A., Aimo, A., Bernardini, S., & Clerico, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010844 · Cited by 28
The critical role of myostatin in differentiation of sheep myoblasts
Liu, C., Li, W., Zhang, X., Zhang, N., He, S., Huang, J., Ge, Y., & Liu, M. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.04.151 · Cited by 24
Loncar, G., Springer, J., Anker, M. S., Doehner, W., & Lainščak, M. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.10.115 · Cited by 24
Myostatin/Activin-A Signaling in the Vessel Wall and Vascular Calcification
Esposito, P. B., Verzola, D., Picciotto, D., Cipriani, L., Viazzi, F. C., & Garibotto, G. (2021) · Cells · doi:10.3390/cells10082070 · Cited by 22
“Moreover, Mstn may play a role in the pathogenesis of diabetic nephropathy and heart failure [35].”
BackgroundSong, T., Manoharan, P., Millay, D. P., Koch, S. E., Rubinstein, J., Heiny, J. A., & Sadayappan, S. (2019) · Skeletal Muscle · doi:10.1186/s13395-019-0189-y · Cited by 22
Kato, A. (2013) · Future Cardiology · doi:10.2217/fca.13.74 · Cited by 22
Springer, J., Adams, V., & Anker, S. D. (2010) · Circulation · doi:10.1161/cir.0b013e3181d0ba8b · Cited by 23
Myostatin: a multifunctional role in human female reproduction and fertility – a short review
Wang, S., Fang, L., Cong, L., Chung, J. P. W., Li, T. C., & Chan, D. Y. L. (2022) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-022-00969-4 · Cited by 20
“MSTN protein levels rise rapidly after ischemia [38] and following aortic constriction(TAC)-induced hypertrophy in mice [39].”
BackgroundMyostatin regulates pituitary development and hepatic IGF1
Czaja, W., Nakamura, Y., Li, N., Eldridge, J. A., DeAvila, D. M., Thompson, T. B., & Rodgers, B. D. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00001.2019 · Cited by 19
Questions and Answers About Myostatin, GDF11, and the Aging Heart
McNally, E. M. (2016) · Circulation Research · doi:10.1161/circresaha.115.307861 · Cited by 21
“Intriguingly, deletion of myostatin specifically in the heart has been shown to block muscle wasting that occurs in cardiac cachexia although others have found that body-wide myostatin deletion renders little change in basal phenotypes.(3,4) GDF11 is the most closely related TGF-β superfamily member to myostatin and s…”
BackgroundMyostatin Is Elevated in Congenital Heart Disease and After Mechanical Unloading
Bish, L. T., George, I., Maybaum, S. W., Yang, J. A., Chen, J. M., & Sweeney, H. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023818 · Cited by 20
“In animals, it has been observed that myostatin is upregulated following infarct in sheep and rats [2,15], volume overload in rats [3], and pressure overload in mice [4].”
The expression and potential functions of placental myostatin
Peiris, H. N., & Mitchell, M. D. (2012) · Placenta · doi:10.1016/j.placenta.2012.06.021 · Cited by 20
The TGFβ superfamily in cardiac dysfunction
Wu, J., Jackson‐Weaver, O., & Xu, J. (2018) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmy007 · Cited by 19
Wang, L., Zheng, Z., Meng, L., Zhu, L., Li, P., Chen, J., & Yang, H. Q. (2020) · Cell Biology and Toxicology · doi:10.1007/s10565-020-09558-w · Cited by 19
Prokopidis, K., Morwani‐Mangnani, J., McDowell, G., Lip, G. Y. H., Venturelli, M., Sankaranarayanan, R., & Isanejad, M. (2024) · European Geriatric Medicine · doi:10.1007/s41999-024-00950-x · Cited by 19
“HF may induce the production of adiponectin and promote lipolysis through elevated levels of natriuretic peptides [60], and concomitantly, may also increase plasma levels of myostatin and proinflammatory cytokines, which are linked to muscle wasting [14, 61].”
BackgroundLi, F., Luo, T., Rong, H., Lu, L., Zhang, L., Zheng, C., Yi, D., Peng, Y., Lei, E., Xiong, X., et al. (2022) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13098 · Cited by 17
“Interestingly, we detected a small amount of myostatin in the KO, which is thought to come from other tissues such as cardiac muscle through circulation.(42) To our knowledge, this is the first evidence that myostatin plays a central role in mediating the deleterious effects of maternal DEHP exposure on skeletal muscl…”
BackgroundKnapp, M., Supruniuk, E., & Górski, J. (2023) · Biomolecules · doi:10.3390/biom13121777 · Cited by 17
“Very strong support for a role of myostatin in the development of heart cachexia in rats and mice was provided by Heineke et al. [95] through the use of two models with either skeletal muscle-restricted or heart-restricted myostatin deprivation Deletion of myostatin from skeletal muscles resulted…”
BackgroundThe Immateriality of Circulating GDF11
Rodgers, B. D. (2016) · Circulation Research · doi:10.1161/circresaha.116.308478 · Cited by 17
Gu, M., Zhou, X., Zhu, L., Gao, Y., Gao, L., Bai, C., Yang, L., & Li, G. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.774185 · Cited by 16
“In addition, deficiency of myostatin does not induce ventricular hypertrophy, compared with wild-type mice (Cohn et al., 2007; Heineke et al., 2010; Butcher et al., 2017).”
ResultTimofte, D. V., Tudor, R. C., Mocanu, V., & Labusca, L. S. (2024) · Nutrients · doi:10.3390/nu16234231 · Cited by 16
Publication trends in cachexia and sarcopenia in elderly heart failure patients
Springer, J., & Anker, S. D. (2016) · Wiener klinische Wochenschrift · doi:10.1007/s00508-016-1126-2 · Cited by 17
Exercise Training and Interventions for Coronary Artery Disease
Fernández-Rubio, H., Vallejo, R., Rodríguez‐Sanz, D., Calvo‐Lobo, C., Vicente-Campos, D., & Chicharro, J. L. (2022) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd9050131 · Cited by 14
Myostatin: genetic variants, therapy and gene doping
Yamada, A. K., Verlengia, R., & Júnior, C. R. B. (2012) · Brazilian Journal of Pharmaceutical Sciences · doi:10.1590/s1984-82502012000300003 · Cited by 13
Upadhya, B., & Kitzman, D. W. (2017) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-017-0219-2 · Cited by 15
“Injection of a myostatin-blocking antibody in mice with pre-existing HF preserved muscle mass [135].”
BackgroundMyostatin as a plausible biomarker for early stage of sarcopenic obesity
Ishibashi, C., Nakanishi, K., Nishida, M., Shinomiya, H., Shinzawa, M., Kanayama, D., Yamamoto, R., Kudo, T., Nagatomo, I., & Yamauchi‐Takihara, K. (2024) · Scientific Reports · doi:10.1038/s41598-024-79534-5 · Cited by 14
Maricelli, J. W., Bishaw, Y. M., Wang, B., Du, ., & Rodgers, B. D. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.158 · Cited by 13
RETRACTED: Cardiovascular Disease and Exercise: From Molecular Mechanisms to Clinical Applications
Wang, B., Gan, L., Deng, Y., Zhu, S., Li, G., Nasser, M. I., Liu, N., & Zhu, P. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11247511 · Cited by 16
“While an increased myostatin expression in cardiomyocytes in heart failure has a cardioprotective effect, it is also one of the causes of skeletal muscle atrophy in heart failure [69,70].”
BackgroundRetractedThe Small Molecule ACM-001 Improves Cardiac Function in a Rat Model of Severe Cancer Cachexia
Poetsch, M. S., Palus, S., Linthout, S. V., von Haehling, S., Doehner, W., Coats, A. J. S., Anker, S. D., & Springer, J. (2023) · European Journal of Heart Failure · doi:10.1002/ejhf.2840 · Cited by 13
Myostatin's marvels: From muscle regulator to diverse implications in health and disease
Sharma, S., & Patil, A. (2024) · Cell Biochemistry and Function · doi:10.1002/cbf.4106 · Cited by 12
Zhong, C., Zeng, X., Yi, X., Yang, Y., Hu, J., Yin, R., & Chen, X. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47030158 · Cited by 11
“…metabolism has been extensively investigated, revealing that it is highly expressed in the skeletal muscle of both embryonic and adult mice [38], where it regulates muscle fiber number and type [40,41], inhibits muscle fiber growth, and, consequently, limits overall muscle mass increase [42–45].”
Caetano-Anollés, K., Mishra, S., & Rodriguez‐Zas, S. L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0116828 · Cited by 11
Yanagisawa, S., Inden, Y., Shimano, M., Yoshida, N., Ishikawa, S., Kato, H., Okumura, S., Miyoshi-Fujii, A., Nagao, T., Yamamoto, T., et al. (2015) · Journal of Interventional Cardiac Electrophysiology · doi:10.1007/s10840-015-0015-3 · Cited by 11
Interplay Between Heart and Skeletal Muscle Disease in Heart Failure
McNally, E. M., & Goldstein, J. A. (2012) · Circulation Research · doi:10.1161/circresaha.111.256776 · Cited by 11
Respiratory muscle weakness in the Zucker diabetic fatty rat
Allwood, M. A., Foster, A., Arkell, A. M., Beaudoin, M., Snook, L. A., Romanova, N. A., Murrant, C. L., Holloway, G. P., Wright, D. C., & Simpson, J. A. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00447.2014 · Cited by 12
Szabó, Z., Vainio, L., Lin, R., Swan, J., Hulmi, J. J., Rahtu‐Korpela, L., Serpi, R., Laitinen, M., Pasternack, A. H., Ritvos, O., et al. (2020) · The FASEB Journal · doi:10.1096/fj.201903074rr · Cited by 11
The Alleviative Effect of Sodium Butyrate on Dexamethasone‐Induced Skeletal Muscle Atrophy
Zhao, X., Zhu, M., Wang, Z., Gao, M., Long, Y., Zhou, S., & Wang, W. (2025) · Cell Biology International · doi:10.1002/cbin.70003 · Cited by 9
“Moreover, drug and gene therapies have been explored, but their application in muscle atrophy treatment is limited by side effects and insufficient efficacy, and no approved drugs have been specifically developed for muscle atrophy treatment (Belizário et al. 2016; Heineke et al. 2010).”
Tamura, Y., Mori, N., Xu, B., Nakamura, T., Yamakoshi, S., Hirose, T., Ito, O., Totsune, K., Takahashi, K., & Kohzuki, M. (2016) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.239.185 · Cited by 10
“To prepare the renal fraction, frozen left kidney was pulverized in liquid nitrogen (Heineke et al. 2010).”
MethodGao, H., Zhang, L., Wang, Z., Yan, K., Zhao, L., & Xiao, W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105765 · Cited by 10
“[75] confirmed that myostatin released from heart tissue during heart failure can strongly regulate skeletal muscle mass.”
BackgroundMyostatin and Activin A as Biomarkers of Sarcopenia in Inflammatory Bowel Disease Patients
Godala, M. M., Gaszyńska, E., Walczak, K., & Małecka-Wojciesko, E. (2024) · Nutrients · doi:10.3390/nu16060810 · Cited by 9
“Increased myocardial MSTN expression was observed after induced myocardial infarction in eight-week-old mice, and its effects, associated with protein degradation and skeletal muscle atrophy, persisted up to two months after myocardial infarction [40].”
BackgroundThe importance of biological sex in cardiac cachexia
Holder, E. R., Alibhai, F. J., Caudle, S. L., McDermott, J. C., & Tobin, S. W. (2022) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00187.2022 · Cited by 9
Dietl, A., Winkel, I., Pietrzyk, G., Paulus, M. G., Bruckmann, A., Schröder, J. A., Sossalla, S. T., Luchner, A., Maier, L. S., & Birner, C. M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0225937 · Cited by 9
“, ligation of coronary arteries[44], transverse aortic constriction[42]) do not display a chronic and gradual progression of heart failure induced myopathy as recently reviewed[8], albeit the assessment of early alterations could indicate new diagnostic or even therapeutic aspects for prevention[41].”
BackgroundMcPherron, A. C. (2013) · Circulation Research · doi:10.1161/circresaha.113.302239 · Cited by 9
Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease
Ju, C., Chen, M., Zhang, J., Lin, Z., & Chen, R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150838 · Cited by 9
“Heineke et al [35] also showed that plasma myostatin levels increased by inducing heart failure in rats with genetic deletion of myostatin in skeletal muscles of rats.”
BackgroundMethodInfluentialKostyunina, D. S., Ivanova, A. D., & Smirnova, О. V. (2018) · Human Physiology · doi:10.1134/s0362119718010127 · Cited by 10
Sarcopenia and Cardiac Dysfunction
Wong, A. K., & Frishman, W. H. (2019) · Cardiology in Review · doi:10.1097/crd.0000000000000285 · Cited by 9
“Preliminary studies of myostatin inhibition have had promising results; however, more research is needed to demonstrate the safety and utility of intervening in these pathways in humans.(62) Hormonal therapies, such as testosterone, ghrelin, growth hormone, and vitamin D, have been proposed as methods for intervention…”
BackgroundLee, S.-J. (2012) · Muscle · doi:10.1016/b978-0-12-381510-1.00079-x · Cited by 8
Deficiency of GDF-11 Accelerates TAC-Induced Heart Failure by Impairing Cardiac Angiogenesis
Zhu, J., Zhang, N., Zhao, Y. F., Liu, Q., Wang, Y., Chen, M., Ma, Q., Dong, A., Wang, Y., & Yu, H. (2023) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2022.11.004 · Cited by 8
Wang, Q., Wang, H., Tian, H., Niu, S., & Xu, R. (2023) · Risk Management and Healthcare Policy · doi:10.2147/rmhp.s412725 · Cited by 8
Picciotto, D., Macciò, L., Verzola, D., Baciga, F., Momentè, C., Russo, E., Viazzi, F. C., Battaglia, Y., & Esposito, P. B. (2024) · Kidney & Blood Pressure Research · doi:10.1159/000539489 · Cited by 9
Rashidlamir, A., Hosseini, S. R. A., Hejazi, K., & Motevalli, M. S. (2016) · Journal of Cardiovascular and Thoracic Research · doi:10.15171/jcvtr.2016.33 · Cited by 8
Liu, Q., Gao, J., Deng, J., & Xiao, J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.593429 · Cited by 8
“The main clinical manifestations of muscle atrophy were chronic progressive distal limb myasthenia and atrophy, hypoesthesia and disappearance of tendon reflex, accompanied by skeletal deformities such as high arch foot and scoliosis (4, 5).”
BackgroundShi, C., Zijlstra, S. N., de Wit, S., Meijers, W. C., Aboumsallem, J. P., Silljé, H. H. W., & de Boer, R. A. (2023) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00223.2023 · Cited by 7
Diagnostic and predictive abilities of myokines in patients with heart failure
Berezin, O. O., Berezina, T. A., Hoppe, U. C., Lichtenauer, M., & Berezin, A. Е. (2024) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2023.12.021 · Cited by 8
Exercise benefits cardiovascular health: from molecular mechanisms to clinical implications
Zhang, X., Li, J., & Gao, F. (2021) · Scientia Sinica Vitae · doi:10.1360/ssv-2020-0359 · Cited by 8
Cardiac Complications: The Understudied Aspect of Cancer Cachexia
Bora, V., & Patel, B. M. (2022) · Cardiovascular Toxicology · doi:10.1007/s12012-022-09727-9 · Cited by 6
Murata, R., Watanabe, H., Nosaki, H., Nishida, K., Maeda, H., Nishida, M., & Maruyama, T. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030562 · Cited by 7
“It has been reported that the inhibition of the atrogin-1 signal improves myocardial atrophy [21] and that myocardial-specific overexpressed myostatin induces myocardial atrophy [41,42].”
BackgroundJu, C., Zhang, J.-H., Chen, M., & Chen, R. (2016) · Biomarkers · doi:10.1080/1354750x.2016.1203999 · Cited by 6
“…about the increases of myostatin in heart failure, previous studies suggested that expressions of myostatin in cardiac cells could be stimulated by the factors related to activation of heart failures, such as mechanical stretch (Wang et al., 2008) and pressure-overload (Heineke et al., 2010).”
BackgroundResultDefining the Roles of Cardiokines in Human Aging and Age-Associated Diseases
Srivastava, H., Pozzoli, M., & Lau, E. (2022) · Frontiers in Aging · doi:10.3389/fragi.2022.884321 · Cited by 6
“Critically, selective deletion of Gdf8/ Mstn in the heart is sufficient to prevent muscle loss in mouse models of heart failure (Heineke et al., 2010), thus suggesting the circulating pool of GDF8/MSTN contributed by the heart functions to regulate the mass of skeletal muscles in an endocrine…”
BackgroundInfluentialCellular mechanisms promoting cachexia and how they are opposed by sirtuins
Samant, S. A., Pillai, V. B., & Gupta, M. P. (2018) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2018-0479 · Cited by 5
“…Journal of Physiology and Pharmacology Draft 8 considered as one of the major marker of muscle atrophy, and is also linked to cardiac cachexia (Heineke et al. 2010), heart failure (George et al. 2010), insulin-resistance (Hittel et al. 2010) and obesity (Hittel et al. 2009).”
BackgroundThe sarcopenia and frailty conundrum in heart failure: a clinical perspective from the FREE registry
Arévalo‐Lorido, J. C., Mayoral-Testón, N., Jarén, E. V., González-Fernández, R., Castellano, B. C., Robles, N. R., Gómez, J. C., Salvador, L. M., & Fernandez-Berges, D. J. (2026) · Acta cardiologica. Supplementum · doi:10.1080/00015385.2026.2664040 · Cited by 4
“Conversely, HF may promote the production of adiponectin and increase lipolysis through elevated natriuretic peptide levels [37] and may also increase plasma levels of myostatin and proinflammatory cytokines, which are linked to muscle wasting [38].”
Liu, R., Xi, Y., Duan, X., Zhao, Y., & Tian, Z. (2025) · Life Sciences · doi:10.1016/j.lfs.2025.123628 · Cited by 4
Yin, L. L., Wu, S., Bai, P., & Wang, X. (2024) · Journal of Proteomics · doi:10.1016/j.jprot.2024.105283 · Cited by 4
Skeletal Muscle Changes in Chronic Cardiac Disease and Failure
Kennel, P. J., MANCINI, D. M., & Schulze, P. C. (2015) · Comprehensive physiology · doi:10.1002/j.2040-4603.2015.tb00653.x · Cited by 4
“Recently, the possible role of myostatin in muscle atrophy in advanced HF has been investigated (74).”
Adipositas und kardiale Kachexie bei chronischer Herzinsuffizienz
Clauser, M., & Altenberger, J. (2013) · Herz · doi:10.1007/s00059-013-3885-0 · Cited by 5
Myostatin: An Overlooked Player in Heart Failure?
Silljé, H. H. W., & de Boer, R. A. (2010) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfq044 · Cited by 4
“myostatin levels also increased during heart failure, most likely as a result of increased production in the heart.(18) Serum myostatin might therefore be placed on a list of potential new biomarkers”
BackgroundLi, J., Fredericks, M., Tang, M., Cannell, M., Joshi, S. R., Kumar, R., André, P., & Suragani, R. N. V. S. (2022) · FEBS Letters · doi:10.1002/1873-3468.14464 · Cited by 3
Guo, W., Pencina, K. M., Gagliano‐Jucá, T., Jasuja, R., Morris, N., O'Connell, K. E., Westmoreland, S. V., & Bhasin, S. (2018) · Journal of the Endocrine Society · doi:10.1210/js.2018-00099 · Cited by 3
“Some studies have reported myocardial hypertrophy in myostatin-null mice [17–19], but others found no significant differences in myocardial mass between wild-type and myostatin-disrupted mice [16, 21, 22].”
BackgroundChiba, A., & Mochizuki, N. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813814-4.00014-6 · Cited by 3
McLean, B. A., & Oudit, G. Y. (2015) · Circulation Research · doi:10.1161/circresaha.115.306124 · Cited by 3
Metadata
- Authors
- Heineke, J., Auger-Messier, M., Xu, J., Sargent, M., York, A., Welle, S., & Molkentin, J. D.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- From the Department of Pediatrics, University of Cincinnati, Cincinnati Children’s Hospital Medical Center, Cincinnati (J.H., M.A.-M., J.X., M.S., A.Y., J.D.M.), and Department of Medicine, University of Rochester, School of Medicine and Dentistry, Rochester, NY (S.W.). Dr Heineke is currently at the Department of Cardiology and Angiology, Cluster of Excellence—Rebirth, Medizinische Hochschule Hannover, Hannover, Germany.
- Venue
- Circulation
- Published
- 2010-01-26
- Volume
- 121
- Issue
- 3
- Pages
- 419-425
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC2823256
- OpenAlex
- W2144331482
- Cited by
- 238
- References
- 28
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 14 · 2023: 11 · 2022: 18 · 2021: 14 · 2020: 11 · 2019: 12 · 2018: 14 · 2017: 16 · 2016: 23 · 2015: 21 · 2014: 10 · 2013: 12 · 2012: 21
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (P01HL069779, R37HL060562, R01HL062927)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Keywords
- myostatin, heart failure, cardiac cachexia, skeletal muscle atrophy, heart as endocrine organ, cardiac hypertrophy, pressure overload
- MeSH terms
- Animals, Antibodies, Cachexia, Heart Failure, Mice, Inbred C57BL, Mice, Mutant Strains, Muscular Atrophy, Organ Specificity, Blotting, Western, Gene Expression, Muscle, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, Myocytes, Cardiac, Mice, Myostatin, Gene Knock-In Techniques
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