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  

作　　者：Rong Chen Shiqing Zhang Fang Liu Lin Xia Chong Wang Siamak Sandoghchian Shotorbani Huaxi Xu Subrata Chakrabarti Tianqing Peng Zhaoliang Su 

机构地区：[1]International Genome Center,Jiangsu University,Zhenjiang 212013,China [2]Institute for Medical Immunology,Jiangsu University,Zhenjiang 212013,China [3]Department of Laboratory Medicine,Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China [4]Department of Immunology,Tabriz University of Medical Sciences,Tabriz 5173957616,Iran [5]Lawson Health Research Institute,London Health Sciences Centre,London,Ontario N6A 5w9,Canada [6]Department of Pathology and Laboratory Medicine,Western University,London,Ontario N6A 5CI,Canada

出　　处：《Acta Pharmaceutica Sinica B》2023年第1期128-141,共14页药学学报（英文版）

基　　金：supported by National Natural Science Foundation of China(Grant No.81871244);Primary Research&Development Plan of Jiangsu Province(BE2019700,China);Jiangsu Province“333”project(BRA2018016,China);six talent peaks project in Jiangsu Province(2019-WSN-122,China);Projects of International Cooperation from Jiangsu(BX2019100,China);international cooperation and exchange from Zhenjiang(GJ2020010,China);key funds from health commission of jiangsu(ZD2021009,China)。

摘　　要：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),CX3CR1lowCCR2lowLy6C-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.

关 键 词：Cardiac resident macrophages Cardiac regeneration Cardiac injury Cardiomyocyte proliferation Myocardial infarction 

分 类 号：R542.2[医药卫生—心血管疾病]