Abstract
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.
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The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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This work was supported by the National Natural Science Foundation of China (No. 81460188 and No. 81960228), Yunnan Provincial Department of Science and Technology-Kunming Medical University Joint Special Project on Applied Basic Research (No. 202001AY070001-118), Geriatric Prevention and Treatment Research Center of Yunnan Provincial Health and Family Planning Commission (No. 2016NS201), Yunnan Health Training Project of High Level Talents (No. L-2017013); and the Ten Thousand Talents Program-Famous Doctor Project of Yunnan Province (No. YNWR-MY-2018-018). Dong Birong Expert Workstation in Yunnan Province (No. 202105AF150032), Yunnan Province Clinical Research Center for Geriatrics (No. 202102AA310002).
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All authors contributed substantially to this manuscript. All authors read and approved the final manuscript. Hong H contributed majorly for this manuscript with participating in all the experiments and writing the manuscript. Ning T participated primarily in the animal model establish and histopathological staining assay; Yan L contributed mainly to the cells culture and all in vitro test; Qian H contributed to the collection of patients’ serum and partly ELISA assays; Qiang C contributed the primary cell culture and data collation and analysis. And Qiang M contributed to conception and design this study and guided the writing of manuscript.
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Huang, H., Tang, N., Li, Y. et al. The role of CNPY2 in endothelial injury and inflammation during the progress of atherosclerosis. J Mol Histol 54, 195–205 (2023). https://doi.org/10.1007/s10735-023-10122-z
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DOI: https://doi.org/10.1007/s10735-023-10122-z