Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
The Key Laboratory of Myocardial Ischaemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang, China.
J Cell Physiol. 2021 Mar;236(3):2058-2069. doi: 10.1002/jcp.29993. Epub 2020 Aug 11.
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-βR1/Smad signalling pathway. This study highlights a new therapeutic strategy for preventing endothelial dysfunction associated with cardiovascular disease.
长链非编码 RNA 反义非编码 RNA 在 INK4 基因座（ANRIL）中发挥着关键作用，在动脉粥样硬化的发生发展中起着关键作用。然而，ANRIL 对血管内皮功能障碍的确切作用尚不清楚。在这项研究中，我们检测了冠心病患者血浆中 ANRIL 的表达，并阐明了其作用的分子机制。我们分析了 ANRIL 与内皮功能障碍标志物之间的相关性。我们还研究了 ANRIL 对调节内皮功能障碍的影响。在急性冠脉综合征患者中，ANRIL 水平升高。ANRIL 的表达与单核细胞趋化蛋白-1 和白细胞介素-10 等炎症细胞因子相关，这些细胞因子是对内皮功能障碍的反应而分泌的。ANRIL 的敲低显著促进了人脐静脉内皮细胞（HUVEC）的增殖和小管形成，抑制了炎症激活和细胞凋亡。ANRIL 介导的 let-7b 抑制通过靶向 TGF-βR1/Smad 信号通路调节 HUVEC 功能障碍。这项研究为预防与心血管疾病相关的内皮功能障碍提供了一种新的治疗策略。
