TY - JOUR
T1 - Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells
AU - Cheng, Min
AU - Yang, Junjie
AU - Zhao, Xiaoqi
AU - Zhang, Eric
AU - Zeng, Qiutang
AU - Yu, Yang
AU - Yang, Liu
AU - Wu, Bangwei
AU - Yi, Guiwen
AU - Mao, Xiaobo
AU - Huang, Kai
AU - Dong, Nianguo
AU - Xie, Min
AU - Limdi, Nita A.
AU - Prabhu, Sumanth D.
AU - Zhang, Jianyi
AU - Qin, Gangjian
N1 - Funding Information:
This work was supported by the Natural Science Foundation of China (Grants No. 81100084 and 81570257 to M.C.); Wuhan Chengguang Program (Grant No. 2014072704011260 to M.C.); the National Key Research and Development Program of China (grant no 2016YFA0101100 to N. D); the National Institute of Health (R01 Grants No. HL093439, HL113541, HL131110, and HL138990 to G.Q.; HL142291 to H.Q and G. Q.; K24 Grant No. HL133373 to N.A.L.); the American Diabetes Association (Grant No. 1-15-BS-148 to G.Q.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062278194&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-08895-7
DO - 10.1038/s41467-019-08895-7
M3 - Article
C2 - 30814518
AN - SCOPUS:85062278194
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 959
ER -