Mesenchymal stem cell-derived extracellular vesicles relieve endothelial cell senescence via recovering CTRP9 upon repressing miR-674-5p in atherosclerosis.
Regen Ther
; 27: 354-364, 2024 Dec.
Article
em En
| MEDLINE
| ID: mdl-38645280
ABSTRACT
Background:
The senescence of endothelial cells is of great importance involving in atherosclerosis (AS) development. Recent studies have proved the protective role of mesenchymal stem cell-derived extracellular vesicles in AS, herein, we further desired to unvei their potential regulatory mechanisms in endothelial cell senescence.Methods:
Senescence induced by H2O2 in primary mouse aortic endothelial cells (MAECs) was evaluated by SA-ß-gal staining. Targeted molecule expression was detected by qRT-PCR and Western blotting. The biological functions of MAECs were determined by CCK-8, flow cytometry, transwell, and tube formation assays. Oxidative injury was assessed by LDH, total and lipid ROS, LPO and MDA levels. The proliferation of adipose-derived mesenchymal stem cell (ADSCs) was analyzed by EdU assay. Effect of ADSCs-derived extracellular vesicles (ADSC-EVs) on AS was investigated in HFD-fed ApoE-/- mice.Results:
miR-674-5p was up-regulated, while C1q/TNF-related protein 9 (CTRP9) was down-regulated in H2O2-induced senescent MAECs. CTRP9 was demonstrated as a target gene of miR-674-5p. miR-674-5p inhibition restrained senescence, oxidative stress, promoted proliferation, migration, and angiogenesis of H2O2-stimulated MAECs via enhancing CTRP9 expression. Moreover, treatment with ADSC-EVs inhibited H2O2-induced senescence and dysfunction of MAECs through regulating miR-674-5p/CTRP9 axis. In the in vivo AS mouse model, ADSC-EVs combination with miR-674-5p silencing slowed down AS progression via up-regulation of CTRP9.Conclusion:
ADSC-EVs repressed endothelial cell senescence and improved dysfunction via promotion of CTRP9 expression upon miR-674-5p deficiency during AS progression, which might provide vital evidence for ADSC-EVs as a promising therapy for AS.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article