Ren, Lingyun; Chen, Shanshan; Yao, Dan; Yan, Hong published the artcile< OxLDL-stimulated macrophage exosomes promote proatherogenic vascular smooth muscle cell viability and invasion via delivering miR-186-5p then inactivating SHIP2 mediated PI3K/AKT/mTOR pathway>, SDS of cas: 6823-69-4, the main research area is lipoprotein macrophage exosome microRNA SHIP2 PI3K AKT atherosclerosis; Atherosclerosis; Exosomes; MiR-186–5p/SHIP2/PI3K/AKT/mTOR; OxLDL-stimulated-macrophages; Vascular smooth muscle cells.
The current study aimed to investigate the implication of microRNA (miRNA) profile in the linkage between oxidized low-d.-lipoprotein (oxLDL)-stimulated-macrophages (MΦ) exosomes and vascular smooth muscle cells (VSMCs) during atherosclerosis. VSMCs were treated by oxLDL-stimulated-MΦ with/without GW4869. MiRNA profile in oxLDL-stimulated-MΦ and untreated-MΦ was detected by microarray, then candidate miRNAs were proposed to RT-qPCR and functional validation in VSMCs. MiR-186-5p mimic/inhibitor was transfected into oxLDL-stimulated-MΦ, then its exosomes were used to VSMCs. Subsequently, miR-186-5p, SHIP2 and PI3K/AKT/mTOR pathway were modified alone or in combination in VSMCs. VSMCs viability, invasion and apoptosis were detected. OxLDL-stimulated-MΦ induced VSMCs viability, invasion, but repressed apoptosis (all P < 0.01); while after GW4869 treatment to delete exosomes, its effect was weakened (all P < 0.05). Totally 45 dysregulated miRNAs were identified in oxLDL-stimulated-MΦ vs. untreated-MΦ. The top-three dysregulated miRNAs (miR-186-5p, miR-21-5p, miR-320b) were elevated in VSMCs after oxLDL-stimulated-MΦ treatment (all P < 0.001); while only miR-186-5p mimic greatly enhanced VSMCs viability and invasion (both P < 0.01). Furthermore, miR-186-5p-overexpressed oxLDL-stimulated-MΦ exosomes promoted VSMCs viability, invasion, repressed apoptosis, while miR-186-5p-knockdown oxLDL-stimulated-MΦ exosomes exhibited opposite effect (all P < 0.05). MiR-186-5p neg. regulated SHIP2 in VSMCs and bound SHIP2 via luciferase-reporter-gene assay (all P < 0.05). SHIP2 overexpression decreased VSMCs viability, invasion, PI3K/AKT/mTOR pathway, increased apoptosis, and attenuated miR-186-5p-overexpression's effect on these functions (all P < 0.05). Besides, PI3K activator (740 Y-P) weakened SHIP2-overexpression's effect on VSMCs viability, invasion and apoptosis (all P < 0.05). In conclusion, oxLDL-stimulated-MΦ exosomes deliver miR-186-5p to inactivate SHIP2 mediated PI3K/AKT/mTOR pathway, then promote cell viability and invasion in VSMCs to accelerate atherosclerosis. Molecular Immunology published new progress about Apoptosis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, SDS of cas: 6823-69-4.
Referemce:
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Imidazole | C3H4N2 – PubChem