Research Paper Volume 12, Issue 16 pp 16294—16303

Circulating exosomal miR-144-3p inhibits the mobilization of endothelial progenitor cells post myocardial infarction via regulating the MMP9 pathway

Yihai Liu1, *, , Jiamin Xu2, *, , Rong Gu2, *, , Zhu Li2, , Kun Wang2, , Yu Qi2, , Xuan Sun2, , Jun Xie2, , Lian Wang2, , Biao Xu1,2, , Lina Kang1,2, ,

  • 1 Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China
  • 2 Department of Cardiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu, China
* Equal contribution

Received: March 28, 2020       Accepted: June 19, 2020       Published: August 25, 2020
How to Cite

Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: The angiogenesis post myocardial infarction (MI) is compromised in diabetes. MiR-144-3p is reported to be highly expressed in circulating exosomes of diabetic patients, implying its role in diabetic complications. However, whether circulating exosomes and enriched miR-144-3p are involved in the impaired neovascularization in diabetes and the underlying mechanism is unclear.

Results: DMexo and miR-144-3p mimic-treated MSCs had elevated miR-144-3p levels and decreased MMP9, Ets1 and PLG expression. The percentage of EPCs were relatively lower in DMexo-treated or agomir-treated MI mice compared with MI mice. Finally, the luciferase assay confirmed the direct binding between miR-144-3p and Ets1.

Conclusion: Exosomal miR-144-3p could impair the mobilization ability of EPCs, which was associated with impaired ischemia-induced neovascularization.

Methods: Circulating exosomes were isolated from Streptozotocin (STZ)-induced mice. In vitro, mesenchymal stem cells (MSCs) were incubated with exosomes from diabetic mice (DMexo), and miR-144-3p mimic or inhibitor. miR-144-3p, and MMP9 pathway were measured using qPCR and immunoblotting. In vivo, MI mice induced by left anterior descending ligation were treated with DMexo, as well as miR-144-3p agomir. Flow cytometry was used to profile endothelial progenitor cells (EPCs) in peripheral blood and bone marrow post 24 hours respectively.


MI: myocardial infarction; STZ: Streptozotocin; MSCs: mesenchymal stem cells; EPCs: endothelial progenitor cells; MMP9: matrix metallopeptidase 9; Ets1: ETS proto-oncogene 1; PLG: plasminogen; BM: bone marrow; sKitL: soluble Kit-ligand; MNCs: mononuclear cells; LAD: left anterior descending coronary artery.