关键词: Endothelial progenitor cells Exosomes LPS Mouse brain microvascular endothelial cells Sepsis miR-126a-5p

Mesh : Exosomes / metabolism Animals Endothelial Progenitor Cells / metabolism MicroRNAs / metabolism genetics Lipopolysaccharides / toxicity Mice Brain / metabolism pathology Endothelial Cells / metabolism Apoptosis Cell Proliferation Microvessels / metabolism Male Sepsis / metabolism Mice, Inbred C57BL

来  源:   DOI:10.1038/s41598-024-69163-3   PDF(Pubmed)

Abstract:
Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury.
摘要:
内皮祖细胞(EPCs)在维持血管健康和帮助修复受损血管中起着至关重要的作用。然而,EPCs来源的外泌体对脂多糖(LPS)引起的血管内皮细胞损伤的具体影响尚不清楚.本研究旨在探讨EPC外泌体在减轻LPS诱导的血管损伤中的潜在益处,并阐明其潜在机制。最初,从小鼠外周血中分离EPCs,并通过流式细胞术和免疫细胞化学证实了它们的身份。随后,使用透射电子显微镜(TEM)和蛋白质印迹分析鉴定源自EPCs的外泌体.通过对脑微血管内皮细胞(BMEC)进行LPS诱导的损伤来诱导脓毒症模型。EPC及其外泌体均显示出BMECs增殖的显着增加,减少细胞凋亡,降低促炎因子(TNF-α,IL-6和caspase-3),并增强了BMEC的发芽和血管生成。值得注意的,外泌体对这些参数有更显著的影响.此外,EPCs和外泌体均表现出显著增加的miR-126a-5p水平,外泌体显示出更实质性的增强。这些发现表明,补充来自EPCs的外泌体miR-126a-5p可以对BMECs提供保护作用,为治疗脓毒症诱导的微血管内皮细胞损伤提供了潜在的治疗选择。
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