Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury
Summary: 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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224004401 |
| _version_ | 1797272443635630080 |
|---|---|
| author | Mary E. Mohr Shuang Li Allison M. Trouten Rebecca A. Stairley Patrick L. Roddy Chun Liu Min Zhang Henry M. Sucov Ge Tao |
| author_facet | Mary E. Mohr Shuang Li Allison M. Trouten Rebecca A. Stairley Patrick L. Roddy Chun Liu Min Zhang Henry M. Sucov Ge Tao |
| author_sort | Mary E. Mohr |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-07T14:28:20Z |
| format | Article |
| id | doaj.art-c4d1855856a54ca195b81969fa860ec8 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-07T14:28:20Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-c4d1855856a54ca195b81969fa860ec82024-03-06T05:28:32ZengElsevieriScience2589-00422024-03-01273109219Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injuryMary E. Mohr0Shuang Li1Allison M. Trouten2Rebecca A. Stairley3Patrick L. Roddy4Chun Liu5Min Zhang6Henry M. Sucov7Ge Tao8Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USAStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USAPediatric Translational Medicine Institute, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, ChinaDepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224004401cardiovascular medicinePhysiologycell biology |
| spellingShingle | Mary E. Mohr Shuang Li Allison M. Trouten Rebecca A. Stairley Patrick L. Roddy Chun Liu Min Zhang Henry M. Sucov Ge Tao Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury iScience cardiovascular medicine Physiology cell biology |
| title | Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury |
| title_full | Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury |
| title_fullStr | Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury |
| title_full_unstemmed | Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury |
| title_short | Cardiomyocyte-fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury |
| title_sort | cardiomyocyte fibroblast interaction regulates ferroptosis and fibrosis after myocardial injury |
| topic | cardiovascular medicine Physiology cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224004401 |
| work_keys_str_mv | AT maryemohr cardiomyocytefibroblastinteractionregulatesferroptosisandfibrosisaftermyocardialinjury AT shuangli cardiomyocytefibroblastinteractionregulatesferroptosisandfibrosisaftermyocardialinjury AT allisonmtrouten cardiomyocytefibroblastinteractionregulatesferroptosisandfibrosisaftermyocardialinjury AT rebeccaastairley cardiomyocytefibroblastinteractionregulatesferroptosisandfibrosisaftermyocardialinjury AT patricklroddy cardiomyocytefibroblastinteractionregulatesferroptosisandfibrosisaftermyocardialinjury AT chunliu cardiomyocytefibroblastinteractionregulatesferroptosisandfibrosisaftermyocardialinjury AT minzhang cardiomyocytefibroblastinteractionregulatesferroptosisandfibrosisaftermyocardialinjury AT henrymsucov cardiomyocytefibroblastinteractionregulatesferroptosisandfibrosisaftermyocardialinjury AT getao cardiomyocytefibroblastinteractionregulatesferroptosisandfibrosisaftermyocardialinjury |