Circulating exosomal miR-144-3p inhibits the mobilization of endothelial progenitor cells post myocardial infarction via regulating the MMP9 pathway
Yihai Liu, Jiamin Xu, Rong Gu, Li Zhu, Kun Wang, Yu Qi, Xuan Sun, Jun Xie, Lian Wang, Biao Xu, Lina Kang
Abstract
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: , 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.