The Role of MCPIP1 in Macrophage Polarization and Cardiac Function Post‐Myocardial Infarction
Abstract Macrophages play a critical role in both initiating and resolving inflammation following MI (myocardial infarction). Their polarization is essential for maintaining cardiac function. This study aims to explore the role of MCPIP1(Monocyte chemotactic protein‐induced protein 1) in regulating...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-07-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202500747 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849427677195272192 |
|---|---|
| author | Xingxu Zhang Yuan Fang Xiaoming Qin Yiwei Zhang Bo Kang Li Zhong Baoxin Liu Jiachen Luo Yidong Wei |
| author_facet | Xingxu Zhang Yuan Fang Xiaoming Qin Yiwei Zhang Bo Kang Li Zhong Baoxin Liu Jiachen Luo Yidong Wei |
| author_sort | Xingxu Zhang |
| collection | DOAJ |
| description | Abstract Macrophages play a critical role in both initiating and resolving inflammation following MI (myocardial infarction). Their polarization is essential for maintaining cardiac function. This study aims to explore the role of MCPIP1(Monocyte chemotactic protein‐induced protein 1) in regulating macrophage polarization and its impact on heart‐spleen interactions during MI recovery. The role of MCPIP1 was investigated using histological staining, RNA sequencing of bone marrow‐derived macrophages, co‐culture experiments, and validated by western blot. Compared to controls, myeloid MCPIP1‐deficient mice had lower survival rates, larger infarction areas, and more severe inflammatory responses after MI. This was due to increased M1 polarization and impaired conversion to the M2 phenotype. Ferroptosis activation in MCPIP1‐deficient macrophages was inhibited by Fer‐1 and PFT‐α, which promoted M2 polarization and fibroblast activation into myofibroblasts. MCPIP1‐deficient MI mice also showed splenomegaly and elevated levels of circulating macrophages, indicating excessive extramedullary hematopoiesis. Splenectomy improved survival rates and reduced infarction size in MCPIP1‐deficient mice. MCPIP1 suppresses the P53/ferroptosis pathway to regulate macrophage polarization and TGF‐β/SMAD3‐mediated fibroblast activation. Its deficiency exacerbates inflammation through abnormal splenic macrophage output, impairing cardiac repair. MCPIP1 is a promising therapeutic target for modulating ferroptosis and heart‐spleen communication to protect cardiac function following MI. |
| format | Article |
| id | doaj-art-395eee92c38d451eabdf6af44420585f |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-395eee92c38d451eabdf6af44420585f2025-08-20T03:28:58ZengWileyAdvanced Science2198-38442025-07-011225n/an/a10.1002/advs.202500747The Role of MCPIP1 in Macrophage Polarization and Cardiac Function Post‐Myocardial InfarctionXingxu Zhang0Yuan Fang1Xiaoming Qin2Yiwei Zhang3Bo Kang4Li Zhong5Baoxin Liu6Jiachen Luo7Yidong Wei8Department of CardiologyShanghai Tenth People's HospitalTongji University School of Medicine301 Middle Yanchang RoadShanghai200072ChinaDepartment of CardiologyShanghai Tenth People's HospitalTongji University School of Medicine301 Middle Yanchang RoadShanghai200072ChinaDepartment of CardiologyShanghai Tenth People's HospitalTongji University School of Medicine301 Middle Yanchang RoadShanghai200072ChinaDepartment of CardiologyShanghai Tenth People's HospitalTongji University School of Medicine301 Middle Yanchang RoadShanghai200072ChinaDepartment of Health Policy and ManagementFielding School of Public HealthUniversity of California650 Charles E Young Dr S Los Angeles CA 90095 United StatesCollege of Osteopathic Medicine of the PacificWestern University of Health Sciences309 E. Second Street Pomona CA 91766 United StatesDepartment of CardiologyShanghai Tenth People's HospitalTongji University School of Medicine301 Middle Yanchang RoadShanghai200072ChinaDepartment of CardiologyShanghai Tenth People's HospitalTongji University School of Medicine301 Middle Yanchang RoadShanghai200072ChinaDepartment of CardiologyShanghai Tenth People's HospitalTongji University School of Medicine301 Middle Yanchang RoadShanghai200072ChinaAbstract Macrophages play a critical role in both initiating and resolving inflammation following MI (myocardial infarction). Their polarization is essential for maintaining cardiac function. This study aims to explore the role of MCPIP1(Monocyte chemotactic protein‐induced protein 1) in regulating macrophage polarization and its impact on heart‐spleen interactions during MI recovery. The role of MCPIP1 was investigated using histological staining, RNA sequencing of bone marrow‐derived macrophages, co‐culture experiments, and validated by western blot. Compared to controls, myeloid MCPIP1‐deficient mice had lower survival rates, larger infarction areas, and more severe inflammatory responses after MI. This was due to increased M1 polarization and impaired conversion to the M2 phenotype. Ferroptosis activation in MCPIP1‐deficient macrophages was inhibited by Fer‐1 and PFT‐α, which promoted M2 polarization and fibroblast activation into myofibroblasts. MCPIP1‐deficient MI mice also showed splenomegaly and elevated levels of circulating macrophages, indicating excessive extramedullary hematopoiesis. Splenectomy improved survival rates and reduced infarction size in MCPIP1‐deficient mice. MCPIP1 suppresses the P53/ferroptosis pathway to regulate macrophage polarization and TGF‐β/SMAD3‐mediated fibroblast activation. Its deficiency exacerbates inflammation through abnormal splenic macrophage output, impairing cardiac repair. MCPIP1 is a promising therapeutic target for modulating ferroptosis and heart‐spleen communication to protect cardiac function following MI.https://doi.org/10.1002/advs.202500747ferroptosisHeart‐spleen axismacrophageMCPIP1 |
| spellingShingle | Xingxu Zhang Yuan Fang Xiaoming Qin Yiwei Zhang Bo Kang Li Zhong Baoxin Liu Jiachen Luo Yidong Wei The Role of MCPIP1 in Macrophage Polarization and Cardiac Function Post‐Myocardial Infarction Advanced Science ferroptosis Heart‐spleen axis macrophage MCPIP1 |
| title | The Role of MCPIP1 in Macrophage Polarization and Cardiac Function Post‐Myocardial Infarction |
| title_full | The Role of MCPIP1 in Macrophage Polarization and Cardiac Function Post‐Myocardial Infarction |
| title_fullStr | The Role of MCPIP1 in Macrophage Polarization and Cardiac Function Post‐Myocardial Infarction |
| title_full_unstemmed | The Role of MCPIP1 in Macrophage Polarization and Cardiac Function Post‐Myocardial Infarction |
| title_short | The Role of MCPIP1 in Macrophage Polarization and Cardiac Function Post‐Myocardial Infarction |
| title_sort | role of mcpip1 in macrophage polarization and cardiac function post myocardial infarction |
| topic | ferroptosis Heart‐spleen axis macrophage MCPIP1 |
| url | https://doi.org/10.1002/advs.202500747 |
| work_keys_str_mv | AT xingxuzhang theroleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT yuanfang theroleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT xiaomingqin theroleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT yiweizhang theroleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT bokang theroleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT lizhong theroleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT baoxinliu theroleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT jiachenluo theroleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT yidongwei theroleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT xingxuzhang roleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT yuanfang roleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT xiaomingqin roleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT yiweizhang roleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT bokang roleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT lizhong roleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT baoxinliu roleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT jiachenluo roleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction AT yidongwei roleofmcpip1inmacrophagepolarizationandcardiacfunctionpostmyocardialinfarction |