Hsa_circ_0004831 downregulation is partially responsible for atorvastatinalleviated human umbilical vein endothelial cell injuries induced by ox-LDL through targeting the miR-182-5p/CXCL12 axis

BMC Cardiovascular Disorders

Weiwei Zhang¹  Jian Lv¹  Yajing Tang¹  Hai Liu¹  Gang Su¹  Guangli Sun²  Haoang Su³ 

[1]Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, 453100, Zhengzhou, China

[2]Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, 453100, Zhengzhou, China

[3]The Second School of Clinical Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, China

关键词: Atorvastatin;    Ox-LDL;    HUVEC;    Hsa_circ_0004831;    MiR-182-5p;    CXCL12;   

DOI  :  10.1186/s12872-021-01998-4

来源: Springer

【 摘 要 】

BackgroundThe dysfunction and injury of human umbilical vein endothelial cells (HUVECs) are key events of atherosclerosis (AS). Atorvastatin (ATV) has been shown to play a protective role on endothelial cells. However, the associated molecular mechanisms remain not fully illustrated.MethodsHUVECs were treated with oxidized low-density lipoprotein (ox-LDL) to mimic the pathological conditions of endothelial cell injury in AS. Cell injuries were assessed according to cell viability, cell apoptosis, cycle progression, oxidative stress and inflammatory responses using CCK-8 assay, flow cytometry assay or commercial kits. The expression of hsa_circ_0004831, miR-182-5p, and C-X-C motif chemokine 12 (CXCL12) mRNA was examined using quantitative real-time PCR (qPCR). The expression of CXCL12 protein was quantitated by western blot. The predicted target relationship between miR-182-5p and hsa_circ_0004831 or CXCL12 was verified by pull-down assay, dual-luciferase reporter assay or RIP assay.ResultsThe expression of hsa_circ_0004831 was upregulated by ox-LDL but downregulated by ATV in HUVECs. ATV promoted cell viability and cell cycle progression but inhibited apoptosis, oxidative stress and inflammation in ox-LDL-treated HUVECs, while the role of ATV was partially reversed by hsa_circ_0004831 overexpression. MiR-182-5p was targeted by hsa_circ_0004831, and hsa_circ_0004831 overexpression-restored apoptosis, oxidative stress and inflammation were blocked by miR-182-5p restoration. Further, CXCL12 was targeted by miR-182-5p, and miR-182-5p inhibition-stimulated apoptosis, oxidative stress and inflammation were lessened by CXCL12 knockdown.ConclusionHsa_circ_0004831-targeted miR-182-5p/CXCL12 regulatory network is one of the pathways by which ATV protects against ox-LDL-induced endothelial injuries.

【 授权许可】

CC BY