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/eIF2 alpha/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.
基金:
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. YNWRMY-2018-018). Dong Birong Expert Workstation in Yunnan Province
(No. 202105AF150032), Yunnan Province Clinical Research Center
for Geriatrics (No. 202102AA310002).
第一作者机构:[1]Kunming Univ Sci & Technol, Fac Life Sci & Technol, Kunming 650500, Peoples R China[2]Kunming Univ Sci & Technol,Affiliated Hosp,Peoples Hosp Yunnan Prov 1,Dept Geriatr Med,Kunming 650032,Peoples R China
通讯作者:
通讯机构:[3]First Peoples Hosp Yunnan Prov,Dept Neurol,Kunming 650032,Peoples R China[4]First Peoples Hosp Yunnan Prov,157 Jinbi Rd,Kunming 650032,Yunnan,Peoples R China
推荐引用方式(GB/T 7714):
Huang Hong,Tang Ning,Li Yan,et al.The role of CNPY2 in endothelial injury and inflammation during the progress of atherosclerosis[J].JOURNAL OF MOLECULAR HISTOLOGY.2023,54(3):195-205.doi:10.1007/s10735-023-10122-z.
APA:
Huang, Hong,Tang, Ning,Li, Yan,Huo, Qian,Chen, Qiang&Meng, Qiang.(2023).The role of CNPY2 in endothelial injury and inflammation during the progress of atherosclerosis.JOURNAL OF MOLECULAR HISTOLOGY,54,(3)
MLA:
Huang, Hong,et al."The role of CNPY2 in endothelial injury and inflammation during the progress of atherosclerosis".JOURNAL OF MOLECULAR HISTOLOGY 54..3(2023):195-205