环状 RNA circHIPK3 作为动脉粥样硬化中自噬和内皮细胞功能障碍的新型环状 RNA 调节剂。
Circular RNA circHIPK3 as a novel circRNA regulator of autophagy and endothelial cell dysfunction in atherosclerosis.
机构信息
Cardiovascular Department, Cangzhou Central Hospital, Cangzhou, Hebei Province, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12849-12858. doi: 10.26355/eurrev_202012_24187.
OBJECTIVE
The aim of the study was to explore the role and mechanism of circHIPK3 in atherosclerosis.
MATERIALS AND METHODS
AS model was constructed in vivo and in vitro for high fat-fed and ox-LDL treatment. RT-PCR was used to assess the level of circHIPK3. The autophagy level of HUVECs was detected by Western blot, transmission electron microscopy, and LC3II fluorescence intensity. HUVECs lipid accumulation was assessed by oil red staining. Luciferase assay was performed to verify the relationship of circRNA and miRNA, miRNA, and target gene.
RESULTS
The expression of circHIPK3 was downregulated in HFD mice, and ox-LDL treated HUVECs. The level of autophagy was decreased in AS, which was reversed by overexpression of circHIPK3. Meanwhile, forced expression of circHIPK3 would reduce the accumulation of lipid in HUVECs.
CONCLUSIONS
CircHIPK3 could inhibit lipid content in ox-LD-treated HUVECs via activating autophagy. This progression mechanism may target the miR-190b/ATG7 signal pathway, which indicates a suitable role in the pathogenesis of atherosclerosis.
目的
本研究旨在探讨 circHIPK3 在动脉粥样硬化中的作用和机制。
材料和方法
体内和体外构建高脂喂养和 ox-LDL 处理的 AS 模型。采用 RT-PCR 检测 circHIPK3 的水平。通过 Western blot、透射电镜和 LC3II 荧光强度检测 HUVECs 的自噬水平。通过油红染色评估 HUVECs 的脂质积累。采用荧光素酶报告实验验证 circRNA 与 miRNA、miRNA 与靶基因的关系。
结果
在 HFD 小鼠和 ox-LDL 处理的 HUVECs 中，circHIPK3 的表达下调。AS 中自噬水平降低，而过表达 circHIPK3 可逆转这一现象。同时，circHIPK3 的强制表达可减少 HUVECs 中的脂质积累。
结论
CircHIPK3 可通过激活自噬抑制 ox-LD 处理的 HUVECs 中的脂质含量。该进展机制可能针对 miR-190b/ATG7 信号通路，表明其在动脉粥样硬化发病机制中具有潜在作用。
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