期刊
LIFE SCIENCES
卷 274, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119249
关键词
Bone marrow-derived mesenchymal stem cells; Atherosclerosis; Exosomes; MicroRNA-125b-5p; Mitogen-activated protein 4 kinase 4
资金
- Subject of Discipline Construction Capacity Improvement Project of Shenzhen Municipal Health and Family Planning Commission [SZXJ2017041]
Exosomal miR-125b-5p from BMSCs inhibits atherosclerotic plaque formation by targeting Map4k4 expression, leading to reduced inflammation, decreased blood lipid levels, smaller plaque areas, increased expression of smooth muscle cell marker α-SMA, as well as inhibition of apoptosis in AS mice.
Background: Accumulating evidence has reported the role of microRNA (miR) on atherosclerosis (AS), while it is unclear about the relationship between microRNA-125b-5p (miR-125b-5p) and AS. Thus, the object of this study was to investigate the impact of exosomal miR-125b-5p targeting mitogen-activated protein 4 kinase 4 (Map4k4) on AS plaque formation. Methods: The AS model was established using a high fat diet in ApoE(-/-) mice. Mouse bone marrow-derived mesenchymal stem cells (BMSCs) were selected and BMSC-exosomes (BMSC-EXO) were extracted and then identified. The targeted relationship between miR-125b-5p and Map4k4 was tested. BMSC-EXO were modified with miR-125b-5p- and Map4k4-related sequences to interfere with AS mice. MiR-125b-5p and Map4k4 expression in AS tissues were tested. The inflammation-related indices, blood lipid, plaque area, apoptosis index, MMP-9 and alpha-SMA expression in mice with AS were measured. Results: BMSCs and BMSC-EXO were successfully isolated. MiR-125b-5p was down-regulated and Map4k4 was up-regulated in aorta tissues from ApoE(-/-) mice after AS modeling, verses those from C57BL/6 mice without modeling. MiR-125b-5p targeted Map4k4. BMSC-EXO increased miR-125b-5p expression and decreased Map4k4 expression. BMSC-EXO/up-regulated miR-125b-5p and down-regulated Map4k4 in exosomes decreased inflammatory reaction, blood lipid, plaque area, MMP-9 expression and increased a-SMA expression, as well as inhibited apoptosis index of AS mice. Conclusion: Functional studies revealed that exosomal miR-125b-5p from BMSCs suppresses atherosclerotic plaque formation via inhibiting Map4k4 expression.
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