GDF11 restores the impaired function of EPCs-MA by promoting autophagy:GDF11 ameliorates endothelial progenitor cell aging by promoting autophagy
Donghua Liu1
Yang Zhang2
Xin Liu2
Qihe Huang2
Xiaofang Zhang2
Rui Yang2
Yue Zhao3
Penghui Li2
Jiayi He1
Kexiao Zhang1
Zhenwei Pan4
Huiwen Liu1
Baofeng Yang5
1.Department of Histology and Embryology,Harbin Medical University,Harbin 150081,China2.Department of Pharmacology,Harbin Medical University(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China,Key Laboratory of Cardiovascular Research,Ministry of Education),Harbin Medical University,Harbin 150081,China3.Department of Pharmacy at the Second Affiliated Hospital,Harbin,150086,China4.Department of Pharmacology,Harbin Medical University(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China,Key Laboratory of Cardiovascular Research,Ministry of Education),Harbin Medical University,Harbin 150081,China;Research Unit of Noninfectious Chronic Diseases in Frigid Zone,Chinese Academy of Medical Sciences,2019RU070,Harbin 150081,China;NHC Key Laboratory of Cell Transplantation,The First Affiliated Hospital of Harbin Medical University,Harbin 150081,China5.Department of Pharmacology,Harbin Medical University(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China,Key Laboratory of Cardiovascular Research,Ministry of Education),Harbin Medical University,Harbin 150081,China;Research Unit of Noninfectious Chronic Diseases in Frigid Zone,Chinese Academy of Medical Sciences,2019RU070,Harbin 150081,China;Translational Medicine Research and Cooperation Center of Northern China,Heilongjiang Academy of Medical Sciences,Harbin 150081,China
摘要：Objective:Our study aimed to assess the effects of Growth and differentiation factor 11(GDF11)on the function of endothelial progenitor cells in middle-age individuals(EPCs-MA)isolated from mouse bone marrow and to explore the mechanistic relationship between GDF11 and age-related ALP impairment.Methods:Bone marrow-derived EPCs were isolated,culture and GDF11 treatment.In vivo,the mice model of myocardial ischemia(MI)was induced by permanent ligation of the left anterior descending coronary artery(LAD)and mice were randomly divided into MI group and EPCs transplantation group(EPCs-Y,EPCs-MA,EPCs-MA/GDF11).The positive effect of GDF11 treatment of EPCs-MA on MI was verified by echocardiography and the average ratio of fibrotic area to left ventricular(LV)area.In vitro,the effect of GDF11 on ameliorating EPCs aging by promoting autophagy was confirmed by transwell assay,immunofluorescence staining,characterization of EPCs ultrastructure through transmission electron microscope(TEM),lysosome imaging and Western blot.Result:Our findings demonstrate that GDF11 enhances the migration capacity of EPCs-MA and improves recovery of impaired cardiac function after myocardial infarction(MI)in mice,with EPCs isolated from young mice(EPCs-Y)as controls.Moreover,GDF11 restored functional phenotypes of EPCs-MA to levels akin to EPCs-Y,promoting the expression of CD31,endogenous NO synthase,and the restoration of von Willebrand factor(vWF)and CDH5 expression patterns,as well as the formation of Weibel-Palade bodies—key organelles for storage and secretion in endothelial cells and EPCs.Furthermore,GDF11 significantly enhanced the autophagic clearance capability of EPCs-MA by promoting ALP.Conclusions:Our results suggest that GDF11 ameliorates cardiac function impairment by restoring the activities of EPCs from aging mice through enhanced ALP.These findings suggest that GDF11 may hold therapeutic potential for improving aging-related conditions associated with declined autophagy.
机标关键词：functioncellagingamelioratesautophagyendothelialepcs-maimpaired
论文发表日期：2024-10-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 212-223 )
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