Renewal of embryonic and neonatal-derived cardiac-resident macrophages in response to environmental cues abrogated their potential to promote cardiomyocyte proliferation <i>via</i> Jagged-1-Notch1.

Rong Chen; Shiqing Zhang; Fang Liu; Lin Xia; Chong Wang; Siamak Sandoghchian Shotorbani; Huaxi XU; Subrata Chakrabarti; Tianqing Peng; Zhaoliang SU

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Renewal of embryonic and neonatal-derived cardiac-resident macrophages in response to environmental cues abrogated their potential to promote cardiomyocyte proliferation via Jagged-1-Notch1.

Author: Rong CHEN ¹ ; Shiqing ZHANG ¹ ; Fang LIU ¹ ; Lin XIA ¹ ; Chong WANG ¹ ; Siamak SANDOGHCHIAN SHOTORBANI ² ; Huaxi XU ¹ ; Subrata CHAKRABARTI ³ ; Tianqing PENG ³ ; Zhaoliang SU ¹
Author Information

1. International Genome Center, Jiangsu University, Zhenjiang 212013, China.
2. Department of Immunology, Tabriz University of Medical Sciences, Tabriz 5173957616, Iran.
3. Lawson Health Research Institute, London Health Sciences Centre, London, Ontario N6A 5W9, Canada.
Publication Type:Journal Article
Keywords: Cardiac injury; Cardiac regeneration; Cardiac resident macrophages; Cardiomyocyte proliferation; Myocardial infarction
From: Acta Pharmaceutica Sinica B 2023;13(1):128-141
CountryChina
Language:English
Abstract: Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX₃CR1⁺CCR2^-Ly6C^-MHCII^- (MP1), CX₃CR1^lowCCR2^lowLy6C^-MHCII^- (MP2), CX₃CR1^-CCR2⁺Ly6C⁺MHCII^- (MP3), and CX₃CR1⁺CCR2^-Ly6C^-MHCII⁺ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.