Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury
© 2024 The Author(s)..
Neonatal mouse hearts have transient renewal capacity, which is lost in juvenile and adult stages. In neonatal mouse hearts, myocardial infarction (MI) causes an initial loss of cardiomyocytes. However, it is unclear which type of regulated cell death (RCD) occurs in stressed cardiomyocytes. In the current studies, we induced MI in neonatal and juvenile mouse hearts and showed that ischemic cardiomyocytes primarily undergo ferroptosis, a non-apoptotic and iron-dependent form of RCD. We demonstrated that cardiac fibroblasts (CFs) protect cardiomyocytes from ferroptosis through paracrine effects and direct cell-cell interaction. CFs show strong resistance to ferroptosis due to high ferritin expression. The fibrogenic activity of CFs, typically considered detrimental to heart function, is negatively regulated by paired-like homeodomain 2 (Pitx2) signaling from cardiomyocytes. In addition, Pitx2 prevents ferroptosis in cardiomyocytes by regulating ferroptotic genes. Understanding the regulatory mechanisms of cardiomyocyte survival and death can identify potentially translatable therapeutic strategies for MI.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
iScience - 27(2024), 3 vom: 15. März, Seite 109219 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mohr, Mary E [VerfasserIn] |
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| Links: |
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| Themen: |
Cardiovascular medicine |
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| Anmerkungen: |
Date Revised 26.03.2024 published: Electronic-eCollection UpdateOf: bioRxiv. 2023 Feb 08;:. - PMID 36798323 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2024.109219 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369592905 |
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| 500 | |a UpdateOf: bioRxiv. 2023 Feb 08;:. - PMID 36798323 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2024 The Author(s). | ||
| 520 | |a Neonatal mouse hearts have transient renewal capacity, which is lost in juvenile and adult stages. In neonatal mouse hearts, myocardial infarction (MI) causes an initial loss of cardiomyocytes. However, it is unclear which type of regulated cell death (RCD) occurs in stressed cardiomyocytes. In the current studies, we induced MI in neonatal and juvenile mouse hearts and showed that ischemic cardiomyocytes primarily undergo ferroptosis, a non-apoptotic and iron-dependent form of RCD. We demonstrated that cardiac fibroblasts (CFs) protect cardiomyocytes from ferroptosis through paracrine effects and direct cell-cell interaction. CFs show strong resistance to ferroptosis due to high ferritin expression. The fibrogenic activity of CFs, typically considered detrimental to heart function, is negatively regulated by paired-like homeodomain 2 (Pitx2) signaling from cardiomyocytes. In addition, Pitx2 prevents ferroptosis in cardiomyocytes by regulating ferroptotic genes. Understanding the regulatory mechanisms of cardiomyocyte survival and death can identify potentially translatable therapeutic strategies for MI | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a cardiovascular medicine | |
| 650 | 4 | |a cell biology | |
| 700 | 1 | |a Li, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Trouten, Allison M |e verfasserin |4 aut | |
| 700 | 1 | |a Stairley, Rebecca A |e verfasserin |4 aut | |
| 700 | 1 | |a Roddy, Patrick L |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Sucov, Henry M |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Ge |e verfasserin |4 aut | |
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