Phoenixin-14 alleviates inflammatory smooth muscle cell-induced endothelial cell dysfunction in vitro
Phoenixin-14 alleviates inflammatory smooth muscle cell-induced endothelial cell dysfunction in vitro
复制标题
Phoenixin-14 在体外减轻炎症平滑肌细胞诱导的内皮细胞功能障碍
DOI：
10.1016/j.cyto.2022.155973
复制
发表时间：
2022
期刊：
影响因子：
3.8
通讯作者：
Chuan Chen
中科院分区：
文献类型：
--
作者：
Cong Ling;Yang Yang;Xiling Hu;Meiqin Cai;Hui Wang;Chuan Chen
颅内动脉瘤(IA)是指颅内动脉局部血管壁受损，形成异常隆起的脑血管疾病。血管内皮细胞(ECs)和血管平滑肌细胞(VSMCs)与IA的形成和破裂密切相关。炎性平滑肌细胞(ISMCs)可导致EC功能障碍并导致IA的进展。菲尼辛-14(PNX-14)是新近发现的一种具有多种功能的脑多肽，参与生殖、心脏保护、脂质沉积和血糖代谢。PNX-14对缺氧缺糖/复氧(OGD/R)诱导的脑血管内皮细胞损伤有保护作用。因此，我们的研究旨在探讨PNX-14对iSMCs诱导的内皮功能障碍的影响。采用周期性机械牵张诱导SMC炎症反应。将人脐静脉内皮细胞暴露于SMC或ISMC条件培养液中，然后用100nM PNX-14处理24 h，用ELISA法检测细胞上清中促炎症细胞因子(IL-1β、IL-6和肿瘤坏死因子-α)的水平。采用CCK-8比色法、流式细胞仪、管形成实验和Transwell迁移实验检测细胞存活率、细胞凋亡率、血管生成和迁移能力。免疫印迹法检测促炎症细胞因子和细胞凋亡标记物(Bcl2、Bax)的蛋白水平。周期性机械牵张可上调SMC中IL-1β、IL-6和肿瘤坏死因子-α水平。用SMC或iSMC条件培养液处理HUVECs可抑制HUVECs的存活率、血管生成和迁移，并诱导细胞凋亡。ISMC条件培养液对细胞功能的影响更为显著。但PNX-14可逆转SMC或ISMC条件培养液对HUVEC生物学功能的影响。PNX-14对SMC培养的人脐静脉内皮细胞的生物学功能无明显影响。PNX-14在体外减轻iSMC诱导的内皮细胞功能障碍。
Intracranial aneurysm (IA) is cerebrovascular disorder which refers to local vessel wall damage to intracranial arteries, forming abnormal bulge. Both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are closely associated with IA formation and rupture. Inflammatory SMCs (iSMCs) were reported to induce EC dysfunction and result in IA progression. Phoenixin-14 (PNX-14) is a recently discovered brain peptide with pleiotropic roles, which participates in reproduction, cardio protection, lipid deposition and blood glucose metabolism. PNX-14 was previously reported to protect brain endothelial cells against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell injury. Therefore, our study was designed to investigate the influence of PNX-14 on iSMCs-induced endothelial dysfunction. Inflammation in SMCs was induced by cyclic mechanical stretch. Human umbilical vein endothelial cells (HUVECs) were exposed to SMC- or iSMC-conditioned medium and then treated with 100 nM PNX-14 for 24 h. The levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) in cell supernatants were analyzed by ELISA. Cell viability, apoptosis, angiogenesis and migration were subjected to CCK-8 assay, flow cytometry analysis, tube formation assay and Transwell migration assay. The protein levels of proinflammatory cytokines and apoptosis markers (Bcl-2 and Bax) were evaluated by western blotting. Cyclic mechanical stretch upregulated IL-1β, IL-6 and TNF-α levels in SMCs. Treatment with SMC- or iSMC-conditioned medium HUVECs inhibited cell viability, angiogenesis and migration and induced apoptosis in HUVECs. iSMC-conditioned medium has more significant effects on cell functions. However, the influence of SMC- or iSMC-conditioned medium treatment on HUVEC biological functions were reversed by PNX-14 treatment. PNX-14 exerts no significant influence on the biological functions of HUVECs treated with SMC medium. PNX-14 alleviates iSMCs-induced endothelial cell dysfunction in vitro.