LncRNA PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis by miR-153-3p/GRB2 axis via ERK/p38 pathway

• Published in: Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2021-11, Vol.31 (12), p.3508-3521
• Main Authors: Guo, Junxia, Li, Jianhua, Zhang, Junbiao, Guo, Xiaoliang, Liu, Hui, Li, Peicheng, Zhang, Yongchun, Lin, Cheng, Fan, Zhenping
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Atherosclerosis; Atherosclerosis - genetics; ERK1/2 and p38 pathway; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Inflammation; Lipoproteins, LDL - metabolism; lncRNA PVT1; MAP Kinase Signaling System; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; miR-153-3p/GRB2 axis; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Small Interfering
• ISSN: 0939-4753; 1590-3729
• DOI: 10.1016/j.numecd.2021.08.031

LncRNA plasmacytoma variant translocation 1 (PVT1) plays a regulatory role in some cardiovascular diseases, but its role in atherosclerosis (AS) remains barely explored. The study aimed to investigate the effects of PVT1 on high fat diet-induced AS and its potential mechanisms. ApoE −/− mice were fed with high fat diet for 8 weeks to establish an AS model. Lentiviral vectors containing PVT1 short hairpin RNA (PVT1-shRNA) or NC-shRNA were administered by tail vein injection. Cell viability, apoptosis, inflammatory factor secretion, and cellular oxidative stress were measured to evaluate oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) injury. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm the interaction between miR-153-3p and PVT1 or growth factor receptor binding protein 2 (GRB2). Atherosclerotic lesions, lipid deposition, and cell apoptosis in aorta were analyzed by H&E, Oil Red O, and TUNEL straining. PVT1 knockdown alleviated ox-LDL-induced inflammation, apoptosis and oxidative stress in HUVECs. PVT1 acted as a sponge of miR-153-3p, and GRB2 was confirmed as a target of miR-153-3p. MiR-153-3p overexpression attenuated the enhanced effects of PVT1 on ox-LDL-induced cell damage. GRB2 overexpression reversed the mitigating effects of miR-153-3p on ox-LDL-caused injury. Inhibiting PVT1 restrained the activation of ERK1/2 and p38 pathway via miR-153-3p/GRB2 axis. Additionally, silencing PVT1 in vivo reduced atherosclerotic plaques, lipid deposition, inflammation, oxidative stress, and apoptosis in AS mice. PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis through miR-153-3p/GRB2 axis via ERK1/2 and p38 pathway. •PVT1 knockdown alleviated ox-LDL-induced inflammation, cell adhesion, apoptosis and oxidative stress in HUVECs.•MiR-153-3p, inversely regulated by PVT1, attenuated the enhanced effects of PVT1 on ox-LDL-induced cell damage.•MiR-153-3p played a protective role in HUVEC damage by restraining GRB2 expression.•PVT1 restrained ox-LDL-induced activation of ERK1/2 and p38 pathway.•PVT1 silence reduced atherosclerotic plaques, lipid deposition, inflammation, oxidative stress and apoptosis in AS mice.