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首页> 外文期刊>Cell biology international. >Bone marrow-derived mesenchymal stem cells microvesicles stabilize atherosclerotic plaques by inhibiting NLRP3-mediated macrophage pyroptosis
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Bone marrow-derived mesenchymal stem cells microvesicles stabilize atherosclerotic plaques by inhibiting NLRP3-mediated macrophage pyroptosis

机译:骨髓衍生的间充质干细胞微泡通过抑制NLRP3介导的巨噬细胞辐射滴眼症稳定动脉粥样硬化斑块

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Rupture of atherosclerotic plaques constitutes the major cause of thrombosis and acute ischemic coronary syndrome. Bone marrow-derived mesenchymal stem cells microvesicles (BMSCs-MVs) are reported to promote angiogenesis. This study investigated the role of BMSCs-MVs in stabilizing atherosclerotic plaques. BMSCs-MVs in mice were isolated and identified. The mouse model of atherosclerosis was established, and mice were injected with BMSCs-MVs via the tail vein. The macrophage model with high glucose and oxidative damage was established and then incubated with BMSCs-MVs. Nod-like receptor protein 3 (NLRP3) expression, pyroptosis-related proteins, and inflammatory factors were detected. Actinomycin D was used to inhibit the secretion of BMSCs-MVs to verify the source of microRNA-223 (miR-223). The binding relationship between miR-223 and NLRP3 was predicted and verified. BMSCs-MVs with knockdown of miR-223 were cocultured with bone marrow-derived macrophages with knockdown of NLRP3, and then levels of miR-223, NLRP3, pyroptosis-related proteins, and inflammatory factors were detected. BMSCs-MVs could reduce the vulnerability index of atherosclerotic plaques and intima-media thickness in mice, and inhibit pyroptosis and inflammation. BMSCs-MVs inhibited pyroptosis and inflammatory factors in macrophages. BMSCs-MVs carried miR-223 to inhibit NLRP3 expression and reduce macrophage pyroptosis, thereby stabilizing the atherosclerotic plaques.
机译:动脉粥样硬化斑块破裂是血栓形成和急性缺血性冠状动脉综合征的主要原因。据报道,骨髓间充质干细胞微泡(BMSCs-MVs)可促进血管生成。本研究探讨了BMSCs-MVs在稳定动脉粥样硬化斑块中的作用。分离并鉴定小鼠骨髓间充质干细胞。建立小鼠动脉粥样硬化模型,经尾静脉注射BMSCs-MVs。建立高糖和氧化损伤的巨噬细胞模型,然后与BMSCs-MVs孵育。检测Nod样受体蛋白3(NLRP3)表达、上睑下垂相关蛋白和炎症因子。放线菌素D用于抑制BMSCs MVs的分泌,以验证microRNA-223(miR-223)的来源。预测并验证了miR-223与NLRP3之间的结合关系。将敲除miR-223的BMSCs-MVs与敲除NLRP3的骨髓源性巨噬细胞共培养,然后检测miR-223、NLRP3、上睑下垂相关蛋白和炎症因子的水平。BMSCs-MVs能降低小鼠动脉粥样硬化斑块的易损性指数和内膜中层厚度,抑制热下垂和炎症反应。BMSCs-MVs抑制巨噬细胞的热下垂和炎症因子。BMSCs-MVs携带miR-223抑制NLRP3表达,减少巨噬细胞热下垂,从而稳定动脉粥样硬化斑块。

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