The lncRNA ANRIL regulates endothelial dysfunction by targeting the let-7b/TGF-βR1 signalling pathway
The lncRNA ANRIL regulates endothelial dysfunction by targeting the let-7b/TGF-βR1 signalling pathway
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lncRNA ANRIL 通过靶向 let-7b/TGF-β R1 信号通路调节内皮功能障碍
DOI：
10.1002/jcp.29993
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发表时间：
2020-08-11
影响因子：
5.6
通讯作者：
Yu, Bo
中科院分区：
文献类型：
--
作者：
Liu, Xianglan;Li, Shufeng;Yu, Bo
INK 4基因座上的长链非编码RNA反义非编码RNA（ANRIL）在动脉粥样硬化的发展中起着关键作用。然而，ANRIL对内皮功能障碍的确切作用仍不清楚。在这项研究中，我们研究了ANRIL在冠状动脉疾病患者中的表达，并阐明了其作用的分子机制。在111例患者的血浆中检测到ANRIL表达。我们分析了ANRIL和内皮功能障碍标志物之间的相关性。我们还研究了ANRIL对内皮功能障碍的调节作用。急性冠脉综合征患者ANRIL水平升高。ANRIL的表达与炎症细胞因子单核细胞趋化蛋白-1和白细胞介素-10相关，这些细胞因子是响应于内皮功能障碍而分泌的。ANRIL的敲除可显著促进人脐静脉内皮细胞（HUVEC）的增殖和小管形成，并抑制炎症激活和凋亡。ANRIL介导的let-7 b抑制通过靶向TGF-β R1/Smad信号通路调节HUVEC功能障碍这项研究强调了一种新的治疗策略，用于预防与心血管疾病相关的内皮功能障碍。
The long noncoding RNA antisense noncoding RNA in the INK4 locus (ANRIL) plays a critical role in the development of atherosclerosis. However, the precise effect of ANRIL on endothelial dysfunction remains unclear. In this study, we investigated ANRIL expression in patients with coronary artery disease and elucidated the molecular mechanism underlying its effect. ANRIL expression was detected in the blood plasma of 111 patients. We analysed the correlation between ANRIL and endothelial dysfunction markers. We also examined the effect of ANRIL on the regulation of endothelial dysfunction. ANRIL levels were increased in patients with acute coronary syndrome. The expression of ANRIL is associated with the inflammatory cytokines monocyte chemoattractant protein-1 and interleukin-10, which are secreted in response to endothelial dysfunction. Knockdown of ANRIL significantly promoted cell proliferation and tubule formation and inhibited inflammatory activation and apoptosis of human umbilical vein endothelial cells (HUVEC). ANRIL-mediated inhibition of let-7b regulates HUVEC dysfunction by targeting the TGF-beta R1/Smad signalling pathway. This study highlights a new therapeutic strategy for preventing endothelial dysfunction associated with cardiovascular disease.