Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy
Disturbances in the ubiquitin proteasome system, and especially changes of the E3 ligases, are subjects of interest when searching for causes and therapies for cardiomyopathies. The aim of this study was to clarify whether the myostatin/AKT/forkhead box O (FOXO) pathway, which regulates the expressi...
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MDPI AG
2022-09-01
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| Online Access: | https://www.mdpi.com/2075-1729/12/9/1418 |
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| author | Lea Hildebrandt Maja-Theresa Dieterlen Kristin Klaeske Josephina Haunschild Diyar Saeed Sandra Eifert Michael A. Borger Khalil Jawad |
| author_facet | Lea Hildebrandt Maja-Theresa Dieterlen Kristin Klaeske Josephina Haunschild Diyar Saeed Sandra Eifert Michael A. Borger Khalil Jawad |
| author_sort | Lea Hildebrandt |
| collection | DOAJ |
| description | Disturbances in the ubiquitin proteasome system, and especially changes of the E3 ligases, are subjects of interest when searching for causes and therapies for cardiomyopathies. The aim of this study was to clarify whether the myostatin/AKT/forkhead box O (FOXO) pathway, which regulates the expression of the E3 ligases muscle atrophy F-box gene (MAFbx) and muscle ring-finger protein-1 (MuRF1), is changed in dilated cardiomyopathy of ischemic origin (IDCM) and dilated cardiomyopathy of non-ischemic origin (NIDCM). The mRNA and protein expression of myostatin, AKT, FOXO1, FOXO3, MAFbx and MuRF1 were quantified by real-time polymerase chain reaction and ELISA, respectively, in myocardial tissue from 26 IDCM and 23 NIDCM patients. Septal tissue from 17 patients undergoing Morrow resection served as a control. MAFbx and FOXO1 mRNA and protein expression (all <i>p</i> < 0.05), AKT mRNA (<i>p</i> < 0.01) and myostatin protein expression (<i>p</i> = 0.02) were decreased in NIDCM patients compared to the control group. Apart from decreases of AKT and MAFbx mRNA expression (both <i>p</i> < 0.01), no significant differences were detected in IDCM patients compared to the control group. Our results demonstrate that the myostatin/AKT/FOXO pathway is altered in NIDCM but not in IDCM patients. FOXO1 seems to be an important drug target for regulating the expression of MAFbx in NIDCM patients. |
| first_indexed | 2024-03-09T23:22:38Z |
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| language | English |
| last_indexed | 2024-03-09T23:22:38Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
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| series | Life |
| spelling | doaj.art-98109ae13b414571afe09b439e5e22592023-11-23T17:23:47ZengMDPI AGLife2075-17292022-09-01129141810.3390/life12091418Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated CardiomyopathyLea Hildebrandt0Maja-Theresa Dieterlen1Kristin Klaeske2Josephina Haunschild3Diyar Saeed4Sandra Eifert5Michael A. Borger6Khalil Jawad7Department of Cardiac Surgery, Heart Center, HELIOS Clinic, University Hospital Leipzig, 04289 Leipzig, GermanyDepartment of Cardiac Surgery, Heart Center, HELIOS Clinic, University Hospital Leipzig, 04289 Leipzig, GermanyDepartment of Cardiac Surgery, Heart Center, HELIOS Clinic, University Hospital Leipzig, 04289 Leipzig, GermanyDepartment of Cardiac Surgery, Heart Center, HELIOS Clinic, University Hospital Leipzig, 04289 Leipzig, GermanyDepartment of Cardiac Surgery, Heart Center, HELIOS Clinic, University Hospital Leipzig, 04289 Leipzig, GermanyDepartment of Cardiac Surgery, Heart Center, HELIOS Clinic, University Hospital Leipzig, 04289 Leipzig, GermanyDepartment of Cardiac Surgery, Heart Center, HELIOS Clinic, University Hospital Leipzig, 04289 Leipzig, GermanyDepartment of Cardiac Surgery, Heart Center, HELIOS Clinic, University Hospital Leipzig, 04289 Leipzig, GermanyDisturbances in the ubiquitin proteasome system, and especially changes of the E3 ligases, are subjects of interest when searching for causes and therapies for cardiomyopathies. The aim of this study was to clarify whether the myostatin/AKT/forkhead box O (FOXO) pathway, which regulates the expression of the E3 ligases muscle atrophy F-box gene (MAFbx) and muscle ring-finger protein-1 (MuRF1), is changed in dilated cardiomyopathy of ischemic origin (IDCM) and dilated cardiomyopathy of non-ischemic origin (NIDCM). The mRNA and protein expression of myostatin, AKT, FOXO1, FOXO3, MAFbx and MuRF1 were quantified by real-time polymerase chain reaction and ELISA, respectively, in myocardial tissue from 26 IDCM and 23 NIDCM patients. Septal tissue from 17 patients undergoing Morrow resection served as a control. MAFbx and FOXO1 mRNA and protein expression (all <i>p</i> < 0.05), AKT mRNA (<i>p</i> < 0.01) and myostatin protein expression (<i>p</i> = 0.02) were decreased in NIDCM patients compared to the control group. Apart from decreases of AKT and MAFbx mRNA expression (both <i>p</i> < 0.01), no significant differences were detected in IDCM patients compared to the control group. Our results demonstrate that the myostatin/AKT/FOXO pathway is altered in NIDCM but not in IDCM patients. FOXO1 seems to be an important drug target for regulating the expression of MAFbx in NIDCM patients.https://www.mdpi.com/2075-1729/12/9/1418heart failurecardiomyopathyprotein breakdownE3 ligasesFOXOMAFbx |
| spellingShingle | Lea Hildebrandt Maja-Theresa Dieterlen Kristin Klaeske Josephina Haunschild Diyar Saeed Sandra Eifert Michael A. Borger Khalil Jawad Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy Life heart failure cardiomyopathy protein breakdown E3 ligases FOXO MAFbx |
| title | Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy |
| title_full | Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy |
| title_fullStr | Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy |
| title_full_unstemmed | Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy |
| title_short | Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy |
| title_sort | myostatin akt foxo signaling is altered in human non ischemic dilated cardiomyopathy |
| topic | heart failure cardiomyopathy protein breakdown E3 ligases FOXO MAFbx |
| url | https://www.mdpi.com/2075-1729/12/9/1418 |
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