Overexpression of MiR-181c-5p Attenuates Human Umbilical Vascular Endothelial Cell Injury in Deep Vein Thrombosis by Targeting FOS

• Published in: International Heart Journal Vol. 64; no. 4; pp. 759 - 767
• Main Authors: Yang, Fei, Chen, Dexiang, Liu, Yi, Zhang, Xumiao, Su, Yang, Zhang, Xialing, Yin, Zhiqiang, Wu, Jiming
• Format: Journal Article
• Language: English
• Published: Japan International Heart Journal Association 29.07.2023; Japan Science and Technology Agency
• Subjects: Apoptosis; Bioinformatics; Cardiovascular diseases; Cell injury; Cell viability; Chromosome 5; Deep venous thrombosis; Endothelial cells; Endothelin 1; Low density lipoprotein; MicroRNA sequencing; MicroRNAs; miRNA; Osteosarcoma; Ox-LDL; Peripheral blood; Therapeutic targets; Thrombosis; Umbilical vein; Deep venous thrombosis; MicroRNA sequencing; Ox-LDL
• ISSN: 1349-2365; 1349-3299
• DOI: 10.1536/ihj.22-689

Deep venous thrombosis (DVT) is the third most common cardiovascular disease. Its clinical therapeutic effect is unsatisfactory due to the high rate of postthrombotic syndrome. Several studies have demonstrated the involvement of miRNAs in DVT. Therefore, we identified differentially expressed miRNAs in patients with DVT and explored their effects and underlying mechanism on endothelial cell (EC) injury.Differentially expressed miRNAs were identified via microRNA sequencing and verified using real-time quantitative PCR. The biological function of miR-181c-5p in human umbilical vein endothelial cell (HUVEC) injury stimulated by oxidized low-density lipoprotein (ox-LDL) was investigated. The target gene of miR-181c-5p was analyzed using bioinformatics and verified via dual-luciferase reporter assay.miRNA sequencing showed that miR-181c-5p was downregulated in the peripheral blood of patients with DVT. Furthermore, miR-181c-5p had a high clinical diagnostic value for DVT by receiver operating characteristic curve analysis. An in vitro cell model of EC injury, miR-181c-5p, was repressed in ox-LDL-treated HUVECs. Enhancing miR-181c-5p expression could alleviate the inhibition cell viability, cell apoptosis, raising ROS and MDA production, the reducing SOD level, and the elevated levels of thrombosis-related factor, ET-1 and vWF induced by ox-LDL. Further analysis revealed that FBJ osteosarcoma oncogene (FOS) is a target of miR-181c-5p and could antagonize the protective role of miR-181c-5p in ox-LDL-induced HUVEC injury.Our research demonstrated that miR-181c-5p could attenuate ox-LDL-induced EC injury and thrombosis-related factor expression by negatively regulating FOS. These findings suggest that the miR-181c-5p/FOS axis is a promising therapeutic target for DVT.