The role of CNPY2 in endothelial injury and inflammation during the progress of atherosclerosis

• DOI: 10.1007/s10735-023-10122-z
• Publication Date: 2023-04-27T06:02:17Z
• Authors: Hong Huang; Ning Tang; Yan Li; Qian Huo; Qiang Chen; Qiang Meng
• Keywords: Inflammation; Mice; Apolipoproteins E; Animals; Endothelial Cells; Apoptosis; Atherosclerosis; Signal Transduction

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.