Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, P.R. China.
Department of Geriatric Medicine, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, 650032, P.R. China.
J Mol Histol. 2023 Jun;54(3):195-205. doi: 10.1007/s10735-023-10122-z. Epub 2023 Apr 27.
Vascular endothelial cells (VECs) injury is closely related to the occurrence and development of atherosclerosis. Canopy FGF signaling regulator 2 (CNPY2), a novel unfolded protein response promoter, has been reported to activate the PERK-CHOP pathway. This study aimed to explore whether CNPY2 is associated with atherosclerosis mediated by VEC injury. By establishing ApoE mouse atherosclerosis model and oxidized low-density lipoprotein (ox-LDL) cell model, we found that CNPY2 was abnormally highly expressed in ApoE mice and ox-LDL-induced mouse aortic endothelial cells (MAECs). Exogenous CNPY2 can significantly aggravate the activation, inflammation, and apoptosis of MAECs induced by ox-LDL and promote the activation of PERK/eIF2α/CHOP signal. The PERK inhibitor GSK2606414 can inhibit CNPY2-induced MAECs injury and PERK signal activation. In addition, in vivo animal experiments furtherly confirmed that CNPY2 could aggravate the process of atherosclerosis in ApoE mice by activating PERK signaling. In conclusion, this study indicated that high level of CNPY2 induces VECs injury by activating PERK signaling and thus participating in the progress of atherosclerosis.
血管内皮细胞（VECs）损伤与动脉粥样硬化的发生和发展密切相关。穹窿形成纤维母细胞生长因子信号调节因子 2（CNPY2）是一种新的未折叠蛋白反应启动子，已被报道能激活 PERK-CHOP 通路。本研究旨在探讨 CNPY2 是否与血管内皮细胞损伤介导的动脉粥样硬化有关。通过建立 ApoE 小鼠动脉粥样硬化模型和氧化型低密度脂蛋白（ox-LDL）细胞模型，我们发现 CNPY2 在 ApoE 小鼠和 ox-LDL 诱导的小鼠主动脉内皮细胞（MAECs）中异常高表达。外源性 CNPY2 可显著加重 ox-LDL 诱导的 MAECs 激活、炎症和凋亡，并促进 PERK/eIF2α/CHOP 信号的激活。PERK 抑制剂 GSK2606414 可抑制 CNPY2 诱导的 MAECs 损伤和 PERK 信号的激活。此外，体内动物实验进一步证实，CNPY2 通过激活 PERK 信号加重 ApoE 小鼠的动脉粥样硬化进程。综上所述，本研究表明高水平的 CNPY2 通过激活 PERK 信号诱导 VECs 损伤，从而参与动脉粥样硬化的进展。
