MicroRNA-216a induces endothelial senescence and inflammation via Smad3/IκBα pathway.
MicroRNA-216a induces endothelial senescence and inflammation via Smad3/IκBα pathway.
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MicroRNA-216a 通过 Smad3/I kappa B α 通路诱导内皮衰老和炎症
DOI：
10.1111/jcmm.13567
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发表时间：
2018-05
影响因子：
5.3
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Yang S;Mi X;Chen Y;Feng C;Hou Z;Hui R;Zhang W
血管内皮细胞衰老在动脉粥样硬化和冠状动脉疾病中起重要作用，但其机制尚不清楚。我们发现，在衰老的内皮细胞中，microRNA-216a(miR-216a)显著增加。建立人脐静脉内皮细胞(HUVECs)复制衰老模型，探讨miR-216a在内皮细胞衰老和功能障碍中的作用。荧光素酶分析表明，Smad3是miR-216a的直接靶标。MiR-216a的稳定表达诱导内皮细胞出现早衰样表型，导致增殖和迁移受损，并通过抑制Smad3的表达进而调节核转录因子κB抑制物α(IκBα)的降解和黏附分子的激活而增加与单核细胞的黏附。相反，抑制衰老的人脐静脉内皮细胞内源性miR-216a可挽救Smad3和IκBα的表达，并抑制单核细胞的黏附。血浆miR-216a在老年冠心病患者(50岁)中显著升高，与匹配的健康对照组(50岁)相比，患冠心病的风险增加31%(优势比1.31，95%可信区间1.03-1.66；P<0.05)。综上所述，我们的数据提示，miR-216a作为Smad3/IκBα途径的内源性抑制物促进内皮衰老和炎症，可能成为治疗衰老相关动脉粥样硬化性疾病的新靶点。
Vascular endothelial senescence contributes to atherosclerosis and coronary artery disease (CAD), but the mechanisms are yet to be clarified. We identified that microRNA‐216a (miR‐216a) significantly increased in senescent endothelial cells. The replicative senescence model of human umbilical vein endothelial cells (HUVECs) was established to explore the role of miR‐216a in endothelial ageing and dysfunction. Luciferase assay indicated that Smad3 was a direct target of miR‐216a. Stable expression of miR‐216a induced a premature senescence‐like phenotype in HUVECs with an impairment in proliferation and migration and led to an increased adhesion to monocytes by inhibiting Smad3 expression and thereafter modulating the degradation of NF‐κB inhibitor alpha (IκBα) and activation of adhesion molecules. Conversely, inhibition of endogenous miR‐216a in senescent HUVECs rescued Smad3 and IκBα expression and inhibited monocytes attachment. Plasma miR‐216a was significantly higher in old CAD patients (>50 years) and associated with increased 31% risk for CAD (odds ratio 1.31, 95% confidence interval 1.03‐1.66; P = .03) compared with the matched healthy controls (>50 years). Taken together, our data suggested that miR‐216a promotes endothelial senescence and inflammation as an endogenous inhibitor of Smad3/IκBα pathway, which might serve as a novel target for ageing‐related atherosclerotic diseases.
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影响因子：
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影响因子：
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