■在动脉粥样硬化病变中，血管壁的广泛炎症导致斑块不稳定。长链非编码RNA（lncRNAs）在动脉粥样硬化的多种生物学过程中发挥重要作用。
■这里，我们旨在确定lncRNA缺氧诱导因子1α-反义RNA2(HIF1A-AS2)在动脉粥样硬化性炎症中的功能作用和调节机制.
■通过高脂饮食(HFD)在ApoE-/-小鼠中诱导动脉粥样硬化小鼠模型。内皮细胞（ECs），将人主动脉平滑肌细胞（SMC）或人冠状动脉内皮细胞（HCAEC）暴露于ox-LDL以建立体外模型。lncRNAHIF1A-AS2对炎症的影响通过测定炎症因子肿瘤坏死因子-α(TNF-α)的水平来评估,白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）和粘附分子血管细胞粘附分子1（VCAM-1）的水平，细胞间粘附分子1(ICAM-1),和巨噬细胞阳离子肽1(MCP-1)。
■已确定lncRNAHIF1A-AS2和ATF2在动脉粥样硬化ApoE-/-小鼠中高表达。在ox-LDL暴露的ECs中下调lncRNAHIF1A-AS2，SMC和HCAECs通过降低促炎因子和粘附分子的水平来抑制炎症。LncRNAHIF1A-AS2与转录因子USF1结合以提高ATF2表达。USF1过表达抵消了lncRNAHIF1A-AS2沉默对ox-LDL诱导的炎症的抑制作用。敲除lncRNAHIF1A-AS2或ATF2也可以减轻动脉粥样硬化小鼠的炎症。总的来说，本研究表明，lncRNAHIF1A-AS2的下调抑制了USF1与ATF2启动子区的结合，然后抑制ATF2的表达，从而抑制动脉粥样硬化炎症。
■该研究表明lncRNAHIF1A-AS2是动脉粥样硬化的有希望的治疗靶标。
UNASSIGNED: In atherosclerotic lesions, extensive inflammation of the vessel wall contributes to plaque instability. Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes in atherosclerosis.
UNASSIGNED: Here, we aim to identify the functional role and regulatory mechanisms of lncRNA hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) in atherosclerotic inflammation.
UNASSIGNED: An atherosclerotic mouse model was induced in ApoE-/- mice by high fat diet (HFD). Endothelial cells (ECs), human aortic smooth muscle cells (SMCs) or human coronary artery endothelial cells (HCAECs) were exposed to ox-LDL to develop the in vitro model. The effects of lncRNA HIF1A-AS2 on inflammation were evaluated by determining levels of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) and levels of adhesion molecules vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and macrophage cationic peptide 1 (MCP-1).
UNASSIGNED: It was established that lncRNA HIF1A-AS2 and ATF2 were highly expressed in atherosclerotic ApoE-/- mice. Downregulating lncRNA HIF1A-AS2 in ox-LDL-exposed ECs, SMCs and HCAECs inhibited inflammation by reducing levels of pro-inflammatory factors and adhesion molecules. LncRNA HIF1A-AS2 bound to the transcription factor USF1 to elevate ATF2 expression. USF1 overexpression counteracted the suppressive effect of lncRNA HIF1A-AS2 silencing on ox-LDL-induced inflammation. Knockdown of lncRNA HIF1A-AS2 or ATF2 could also attenuate inflammation in atherosclerotic mice. Collectively, the present study demonstrates that downregulation of lncRNA HIF1A-AS2 represses the binding of USF1 to the ATF2 promoter region and then inhibits ATF2 expression, thereby suppressing atherosclerotic inflammation.
UNASSIGNED: This study suggests lncRNA HIF1A-AS2 as an promising therapeutic target for atherosclerosis.
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