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Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells

Author

Listed:
  • Min Cheng

    (Huazhong University of Science and Technology)

  • Junjie Yang

    (University of Alabama at Birmingham, School of Medicine and School of Engineering)

  • Xiaoqi Zhao

    (Huazhong University of Science and Technology)

  • Eric Zhang

    (University of Alabama at Birmingham, School of Medicine and School of Engineering)

  • Qiutang Zeng

    (Huazhong University of Science and Technology)

  • Yang Yu

    (University of Alabama at Birmingham, School of Medicine and School of Engineering)

  • Liu Yang

    (Huazhong University of Science and Technology
    University of Alabama at Birmingham, School of Medicine and School of Engineering)

  • Bangwei Wu

    (Fudan University)

  • Guiwen Yi

    (Huazhong University of Science and Technology)

  • Xiaobo Mao

    (Huazhong University of Science and Technology)

  • Kai Huang

    (Huazhong University of Science and Technology)

  • Nianguo Dong

    (Huazhong University of Science and Technology)

  • Min Xie

    (University of Alabama at Birmingham, School of Medicine)

  • Nita A. Limdi

    (University of Alabama at Birmingham, School of Medicine)

  • Sumanth D. Prabhu

    (University of Alabama at Birmingham, School of Medicine)

  • Jianyi Zhang

    (University of Alabama at Birmingham, School of Medicine and School of Engineering)

  • Gangjian Qin

    (University of Alabama at Birmingham, School of Medicine and School of Engineering)

Abstract

Myocardial microRNAs (myo-miRs) are released into the circulation after acute myocardial infarction (AMI). How they impact remote organs is however largely unknown. Here we show that circulating myo-miRs are carried in exosomes and mediate functional crosstalk between the ischemic heart and the bone marrow (BM). In mice, we find that AMI is accompanied by an increase in circulating levels of myo-miRs, with miR-1, 208, and 499 predominantly in circulating exosomes and miR-133 in the non-exosomal component. Myo-miRs are imported selectively to peripheral organs and preferentially to the BM. Exosomes mediate the transfer of myo-miRs to BM mononuclear cells (MNCs), where myo-miRs downregulate CXCR4 expression. Injection of exosomes isolated from AMI mice into wild-type mice downregulates CXCR4 expression in BM-MNCs and increases the number of circulating progenitor cells. Thus, we propose that myo-miRs carried in circulating exosomes allow a systemic response to cardiac injury that may be leveraged for cardiac repair.

Suggested Citation

  • Min Cheng & Junjie Yang & Xiaoqi Zhao & Eric Zhang & Qiutang Zeng & Yang Yu & Liu Yang & Bangwei Wu & Guiwen Yi & Xiaobo Mao & Kai Huang & Nianguo Dong & Min Xie & Nita A. Limdi & Sumanth D. Prabhu & , 2019. "Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08895-7
    DOI: 10.1038/s41467-019-08895-7
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