Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities
Macrophages are known to support cardiac development and homeostasis, contributing to tissue remodeling and repair in the adult heart. However, it remains unclear whether embryonic macrophages also respond to abnormalities in the developing heart. Previously, we reported that the structural protein...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1525931/full |
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| author | Beibei Hu Xiangyang Liu Xiangyang Liu Xiangyang Liu Shanshan Xiong Qin Gong Junjie Yang Hongjun Shi Hongjun Shi Hongjun Shi Min Zhang Fei Liang Zhen Zhang Zhen Zhang |
| author_facet | Beibei Hu Xiangyang Liu Xiangyang Liu Xiangyang Liu Shanshan Xiong Qin Gong Junjie Yang Hongjun Shi Hongjun Shi Hongjun Shi Min Zhang Fei Liang Zhen Zhang Zhen Zhang |
| author_sort | Beibei Hu |
| collection | DOAJ |
| description | Macrophages are known to support cardiac development and homeostasis, contributing to tissue remodeling and repair in the adult heart. However, it remains unclear whether embryonic macrophages also respond to abnormalities in the developing heart. Previously, we reported that the structural protein Sorbs2 promotes the development of the second heart field, with its deficiency resulting in atrial septal defects (ASD). In analyzing RNA-seq data, we noted an upregulation of macrophage-related genes in Sorbs2−/− hearts. Immunostaining and lineage-tracing confirmed an increase in macrophage numbers, underscoring a macrophage response to myocardial abnormalities. Partial depletion of macrophages led to downregulation of genes involved in lipid metabolism, muscle development and organ regeneration, alongside upregulation of genes associated with DNA damage-induced senescence and cardiomyopathy. Additionally, a non-significant increase in septal defects in macrophage-depleted Sorbs2−/− hearts suggests a potential reparative function for macrophages in maintaining structural integrity. Valve formation, however, remained unaffected. Our findings suggest that embryonic macrophages might sense abnormalities in embryonic cardiomyocytes and could adaptively support cardiac structure and function development in response to myocardial abnormalities. |
| format | Article |
| id | doaj-art-cd946a1d740e4c1daa84b9ca8ffbc31f |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-cd946a1d740e4c1daa84b9ca8ffbc31f2025-01-15T06:10:39ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011510.3389/fgene.2024.15259311525931Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalitiesBeibei Hu0Xiangyang Liu1Xiangyang Liu2Xiangyang Liu3Shanshan Xiong4Qin Gong5Junjie Yang6Hongjun Shi7Hongjun Shi8Hongjun Shi9Min Zhang10Fei Liang11Zhen Zhang12Zhen Zhang13Pediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSchool of Medicine, Westlake University, Hangzhou, Zhejiang, ChinaWestlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, ChinaWestlake Institute for Advanced Study, Hangzhou, Zhejiang, ChinaPediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai United International School (Gubei Campus), Shanghai, ChinaPediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSchool of Medicine, Westlake University, Hangzhou, Zhejiang, ChinaWestlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, ChinaWestlake Institute for Advanced Study, Hangzhou, Zhejiang, ChinaPediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaNeonatal Intensive Care Unit, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaPediatric Translational Medicine Institute and Pediatric Congenital Heart Disease Institute, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Collaborative Innovative Center of Intelligent Medical Device and Active Health, Shanghai University of Medicine and Health Sciences, Shanghai, ChinaMacrophages are known to support cardiac development and homeostasis, contributing to tissue remodeling and repair in the adult heart. However, it remains unclear whether embryonic macrophages also respond to abnormalities in the developing heart. Previously, we reported that the structural protein Sorbs2 promotes the development of the second heart field, with its deficiency resulting in atrial septal defects (ASD). In analyzing RNA-seq data, we noted an upregulation of macrophage-related genes in Sorbs2−/− hearts. Immunostaining and lineage-tracing confirmed an increase in macrophage numbers, underscoring a macrophage response to myocardial abnormalities. Partial depletion of macrophages led to downregulation of genes involved in lipid metabolism, muscle development and organ regeneration, alongside upregulation of genes associated with DNA damage-induced senescence and cardiomyopathy. Additionally, a non-significant increase in septal defects in macrophage-depleted Sorbs2−/− hearts suggests a potential reparative function for macrophages in maintaining structural integrity. Valve formation, however, remained unaffected. Our findings suggest that embryonic macrophages might sense abnormalities in embryonic cardiomyocytes and could adaptively support cardiac structure and function development in response to myocardial abnormalities.https://www.frontiersin.org/articles/10.3389/fgene.2024.1525931/fullmacrophageSorbs2cardiac septal defectvalve formationadaptive response |
| spellingShingle | Beibei Hu Xiangyang Liu Xiangyang Liu Xiangyang Liu Shanshan Xiong Qin Gong Junjie Yang Hongjun Shi Hongjun Shi Hongjun Shi Min Zhang Fei Liang Zhen Zhang Zhen Zhang Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities Frontiers in Genetics macrophage Sorbs2 cardiac septal defect valve formation adaptive response |
| title | Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities |
| title_full | Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities |
| title_fullStr | Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities |
| title_full_unstemmed | Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities |
| title_short | Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities |
| title_sort | increased cardiac macrophages in sorbs2 deficient hearts revealing a potential role for macrophage in responding to embryonic myocardial abnormalities |
| topic | macrophage Sorbs2 cardiac septal defect valve formation adaptive response |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1525931/full |
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