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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. [ABSTRACT FROM AUTHOR]

Background: Cerebral ischemia/reperfusion (I/R) injury leads to cerebrovascular dysfunction characterized by endothelial cell injury or death. Metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has been reported to be associated with endothelial dysfunction. Our study aimed to investigate the effect of MALAT1 on vascular endothelium. Methods: In this study, oxygen-glucose deprivation and reoxygenation (OGD-R) were used as in vitro studies to investigate the role of MALAT1 in I/R-induced apoptosis of cerebrovascular endothelial cells in an I/R injury model. Primary human brain microvascular endothelial cells were cultured on the condition of OGD-R and MALAT1 expression levels and apoptosis were measured at 6, 9, 12, 24 and 36 h after reoxygenation. The expression of MALAT1 and the apoptosis rate of cells exposed to OGD-R showed the trend of reoxygenation. The kit detected the expression of ROS and PI3K, and the change of Akt signal was detected by Western-blot. Results: After OGD-R, over-expression of MALAT1 lentivirus increased phosphatidylinositol 3-kinase (PI3K) activity and activation of Akt phosphorylation, while decreased apoptosis and caspase 3 activity. Moreover, these effects could be successfully eliminated by treating with a PI3K inhibitor (wortmannin). In contrast, knockdown of MALAT1 lentivirus reduced PI3K activity and Akt phosphorylation, while increased apoptosis and caspase 3 activity. Overexpression or knockdown of MALAT1 had no significant effect on that OGD-R-induced reactive oxygen species (ROS) production. Conclusions: This study first proposed that lncRNA MALAT1 can protect human cerebrovascular endothelial cells from OGD-R-induced apoptosis through a PI3K-dependent mechanism. These findings suggest that MALAT1 may be a potential new therapeutic target for brain I/R injury. [ABSTRACT FROM AUTHOR]