Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing 210008, China.
Department of Cardiology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, Jiangsu, China.
Aging (Albany NY). 2020 Aug 25;12(16):16294-16303. doi: 10.18632/aging.103651.
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.
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.
Exosomal miR-144-3p could impair the mobilization ability of EPCs, which was associated with impaired ischemia-induced neovascularization.
Circulating exosomes were isolated from Streptozotocin (STZ)-induced mice. , 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. , 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.
心肌梗死后（MI）的血管生成在糖尿病中受损。据报道，miR-144-3p 在糖尿病患者循环的外泌体中高度表达，暗示其在糖尿病并发症中的作用。然而，循环外泌体和富含 miR-144-3p 是否参与糖尿病中受损的新生血管形成以及潜在的机制尚不清楚。
DMexo 和 miR-144-3p 模拟物处理的间充质干细胞（MSCs）具有更高水平的 miR-144-3p 和降低的 MMP9、Ets1 和 PLG 表达。与 MI 小鼠相比，DMexo 处理或 agomir 处理的 MI 小鼠中 EPCs 的比例相对较低。最后，荧光素酶测定证实了 miR-144-3p 与 Ets1 之间的直接结合。
外泌体 miR-144-3p 可能损害 EPC 的动员能力，这与缺血诱导的新生血管形成受损有关。
从链脲佐菌素（STZ）诱导的小鼠中分离循环外泌体。将间充质干细胞（MSCs）与来自糖尿病小鼠（DMexo）的外泌体以及 miR-144-3p 模拟物或抑制剂孵育。使用 qPCR 和免疫印迹测量 miR-144-3p 和 MMP9 途径。用左前降支结扎诱导 MI 小鼠，并用 DMexo 以及 miR-144-3p agomir 处理。分别在 24 小时后通过流式细胞术对外周血和骨髓中的内皮祖细胞（EPCs）进行分析。
