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ORIGINAL RESEARCH article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1525931
This article is part of the Research Topic Recent Advances in Causes, Diagnosis, and Therapeutics for Congenital Heart Defects View all 14 articles

Increased cardiac macrophages in Sorbs2-deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities

Provisionally accepted
Zhen Zhang Zhen Zhang 1*Beibei Hu Beibei Hu 1Xiangyang Liu Xiangyang Liu 2*Shanshan Xiong Shanshan Xiong 1*Qin Gong Qin Gong 3*Junjie Yang Junjie Yang 1*Hongjun Shi Hongjun Shi 2*Min Zhang Min Zhang 1Fei Liang Fei Liang 1*
  • 1 Shanghai Children's Medical Center, Shanghai, China
  • 2 Westlake University, Hangzhou, Zhejiang, China
  • 3 Shanghai United International School, Shanghai, China

The final, formatted version of the article will be published soon.

    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.

    Keywords: macrophage, Sorbs2, Cardiac septal defect, Valve formation, adaptive response

    Received: 10 Nov 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Zhang, Hu, Liu, Xiong, Gong, Yang, Shi, Zhang and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zhen Zhang, Shanghai Children's Medical Center, Shanghai, China
    Xiangyang Liu, Westlake University, Hangzhou, 310024, Zhejiang, China
    Shanshan Xiong, Shanghai Children's Medical Center, Shanghai, China
    Qin Gong, Shanghai United International School, Shanghai, China
    Junjie Yang, Shanghai Children's Medical Center, Shanghai, China
    Hongjun Shi, Westlake University, Hangzhou, 310024, Zhejiang, China
    Fei Liang, Shanghai Children's Medical Center, Shanghai, China

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