脐带间充质干细胞来源的外泌体miRNAs延缓血管内皮细胞衰老和抑制动脉粥样硬化形成的分子机制研究

延缓血管内皮细胞衰老是防治动脉粥样硬化的重要策略。本项目前期研究发现，脐带间充质干细胞来源的外泌体（hucMSC-exo）可显著延缓血管内皮细胞衰老；miR-21-5p和miR-143-3p等miRNAs在hucMSC-exo中具有较高丰度，且在血管内皮细胞中沉默或过表达这些miRNAs可显著影响细胞衰老。然而有关这些hucMSC-exo-miRNAs影响血管内皮细胞衰老的作用机制及其在体内是否具有同样的作用尚不清楚。为此，本项目拟在明确hucMSC-exo介导这些miRNAs影响血管内皮细胞衰老的基础上，鉴定其下游靶基因，探讨这些外泌体miRNAs调控靶基因延缓血管内皮细胞衰老的潜在机制，最后在动物水平上深入研究它们对血管衰老和动脉粥样硬化的影响及其作用机制。本研究有助于揭示hucMSC-exo-miRNAs对血管内皮细胞衰老的调控机制，并为预防和治疗动脉粥样硬化提供新的思路和应对策略。

Delaying the senescence of vascular endothelial cells is an important strategy for the prevention and treatment of atherosclerosis (AS). We previously demonstrated that the exosomes secreted by human umbilical cord mesenchymal stem cells (hucMSC-exo) could significantly delay endothelial cell senescence; several miRNAs including miR-21-5p and miR-143-3p were highly abundant in hucMSC-exo. Further investigation unveiled that changing the expression of these miRNAs significantly delayed the senescence of vascular endothelial cells. However, the underlying mechanisms of these hucMSC-exosomal miRNAs (hucMSC-exo-miRNAs) on endothelial cell senescence and whether they have the same effect in vivo are still unknown. This project aims to probe into the effect of these hucMSC-exo-miRNAs on endothelial cell senescence, identify the targets of hucMSC-exo-miRNAs, and then explore the underlying mechanism of hucMSC-exo-miRNAs affecting endothelial cell senescence; finally, we will dig into the functional roles of hucMSC-exo-miRNAs on vascular aging and AS development in vivo. This study will contribute to clarify the molecular mechanism of hucMSC-exo-miRNAs regulating endothelial cell senescence, and provide novel strategies for the prevention and treatment of atherosclerosis.