PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: Senescence induced by H2O2 in primary mouse aortic endothelial cells (MAECs) was evaluated by SA-β-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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Senescence induced by H2O2 in primary mouse aortic endothelial cells (MAECs) was evaluated by SA-β-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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■内皮细胞的衰老在动脉粥样硬化（AS）的发展中非常重要。最近的研究证明了间充质干细胞来源的细胞外囊泡在AS中的保护作用,在这里，我们进一步希望揭示它们在内皮细胞衰老中的潜在调节机制。
■通过SA-β-gal染色评估H2O2在原代小鼠主动脉内皮细胞(MAEC)中诱导的衰老。通过qRT-PCR和Western印迹检测靶向分子表达。通过CCK-8、流式细胞术、transwell,和试管形成测定。通过LDH评估氧化损伤，总和脂质ROS，LPO和MDA水平。采用EdU法检测脂肪间充质干细胞(ADSCs)的增殖情况。在HFD喂养的ApoE-/-小鼠中研究了ADSC衍生的细胞外囊泡(ADSC-EV)对AS的影响。
■miR-674-5p上调，而C1q/TNF相关蛋白9（CTRP9）在H2O2诱导的衰老MAECs中下调。CTRP9被证明是miR-674-5p的靶基因。miR-674-5p抑制衰老,氧化应激，促进扩散，迁移,通过增强CTRP9的表达，H2O2刺激的MAECs血管生成。此外，ADSC-EV治疗通过调节miR-674-5p/CTRP9轴抑制H2O2诱导的MAECs衰老和功能障碍。在体内AS小鼠模型中，ADSC-EV与miR-674-5p沉默的组合通过上调CTRP9减缓AS进展。
■ADSC-EV在AS进展期间miR-674-5p缺乏时通过促进CTRP9表达抑制内皮细胞衰老并改善功能障碍，这可能为ADSC-EV作为一种有前途的AS治疗提供重要证据。
■通过SA-β-gal染色评估H2O2在原代小鼠主动脉内皮细胞(MAEC)中诱导的衰老。通过qRT-PCR和Western印迹检测靶向分子表达。通过CCK-8、流式细胞术、transwell,和试管形成测定。通过LDH评估氧化损伤，总和脂质ROS，LPO和MDA水平。采用EdU法检测脂肪间充质干细胞(ADSCs)的增殖情况。在HFD喂养的ApoE-/-小鼠中研究了ADSC衍生的细胞外囊泡(ADSC-EV)对AS的影响。
■miR-674-5p上调，而C1q/TNF相关蛋白9（CTRP9）在H2O2诱导的衰老MAECs中下调。CTRP9被证明是miR-674-5p的靶基因。miR-674-5p抑制衰老,氧化应激，促进扩散，迁移,通过增强CTRP9的表达，H2O2刺激的MAECs血管生成。此外，ADSC-EV治疗通过调节miR-674-5p/CTRP9轴抑制H2O2诱导的MAECs衰老和功能障碍。在体内AS小鼠模型中，ADSC-EV与miR-674-5p沉默的组合通过上调CTRP9减缓AS进展。
■ADSC-EV在AS进展期间miR-674-5p缺乏时通过促进CTRP9表达抑制内皮细胞衰老并改善功能障碍，这可能为ADSC-EV作为一种有前途的AS治疗提供重要证据。
