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Volume 4 Issue 4
Oct.  2024
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Article Navigation >  Frigid Zone Medicine  > 2024  >  4(4): 212-223
Donghua Liu, Yang Zhang, Xin Liu, Qihe Huang, Xiaofang Zhang, Rui Yang, Yue Zhao, Penghui Li, Jiayi He, Kexiao Zhang, Zhenwei Pan, Huiwen Liu, Baofeng Yang. GDF11 restores the impaired function of EPCs-MA by promoting autophagy: GDF11 ameliorates endothelial progenitor cell aging by promoting autophagy[J]. Frigid Zone Medicine, 2024, 4(4): 212-223. doi: 10.1515/fzm-2024-0021
Citation: Donghua Liu, Yang Zhang, Xin Liu, Qihe Huang, Xiaofang Zhang, Rui Yang, Yue Zhao, Penghui Li, Jiayi He, Kexiao Zhang, Zhenwei Pan, Huiwen Liu, Baofeng Yang. GDF11 restores the impaired function of EPCs-MA by promoting autophagy: GDF11 ameliorates endothelial progenitor cell aging by promoting autophagy[J]. Frigid Zone Medicine, 2024, 4(4): 212-223. doi: 10.1515/fzm-2024-0021
shu

GDF11 restores the impaired function of EPCs-MA by promoting autophagy: GDF11 ameliorates endothelial progenitor cell aging by promoting autophagy

doi: 10.1515/fzm-2024-0021
  • 1.

    Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China

  • 2.

    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

  • 3.

    Department of Pharmacy at the Second Affiliated Hospital, Harbin, 150086, China

  • 4.

    Research Unit of Noninfectious Chronic Diseases in Frigid Zone, Chinese Academy of Medical Sciences, 2019RU070, Harbin 150081, China

  • 5.

    NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin 150081, China

  • 6.

    Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150081, China

Funds:

Creative Research Groups of the National Natural Science Foundation of China 81421063

China Postdoctoral Science Foundation 2016M591556

Natural Science Foundation of Heilongjiang Province of China H2016008

Postdoctoral Science Foundation of Heilongjiang Province of China LBH-Z15146

Research Project of the Health and Family Planning Commission of Heilongjiang Province 2016-166

More Information
    Abstract
  •   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.

     

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