Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Department of General Surgery, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, P.R. China.
Biosci Rep. 2018 Dec 21;38(6). doi: 10.1042/BSR20180598.
Lower extremity deep vein thrombosis (LEDVT), a common peripheral vascular disease caused by a blood clot in a deep vein is usually accompanied by swelling of the lower limbs. MicroRNAs (miRs) have been reported to play roles in LEDVT. We aimed to investigate the effect of miR-495 on LEDVT via toll-like receptor 4 (TLR4) signaling pathway through interleukin 1 receptor type 1 (IL1R1). LEDVT mouse model was established, and the femoral vein (FV) tissues were collected to detect expressions of miR-495, IL1R1, and TLR4 signaling-related genes. The expressions of both CD31 and CD34 (markers for endothelial progenitor cells) in the FV endothelial cells as well as the proportion of CD31/CD34 cells in peripheral blood were measured in order to evaluate thrombosis. The effect of miR-495 on cell viability, cell cycle, and apoptosis was analyzed. IL1R1 was confirmed as the target gene of miR-495. Besides, inhibiting the miR-495 expression could increase IL1R1 expression along with activating the TLR4 signaling pathway. The total number of the leukocytes along with the ratio of weight to length of thrombus in the FV tissue showed an increase. The overexpression of miR-495 could promote FV endothelial cell viability. By injecting agomiR-495 and antagomiR-495 , the number of leukocytes in the FV tissues and the ratio of weight to length of thrombus were significantly decreased in the mice injected with the overexpressed miR-495, and the IL1R1/TLR4 signaling pathway was inhibited. Collectively, overexpressed miR-495 directly promotes proliferation while simultaneously inhibiting apoptosis of FV endothelial cells, alleviating FV thrombosis by inhibiting IL1R1 via suppression of TLR4 signaling pathway.
下肢深静脉血栓形成（LEDVT）是一种常见的外周血管疾病，由深静脉中的血栓引起，通常伴有下肢肿胀。研究表明，微小 RNA（miRs）在 LEDVT 中发挥作用。我们旨在通过白细胞介素 1 受体 1（IL1R1）研究 miR-495 通过 toll 样受体 4（TLR4）信号通路对 LEDVT 的影响。建立 LEDVT 小鼠模型，收集股静脉（FV）组织，检测 miR-495、IL1R1 和 TLR4 信号通路相关基因的表达。测量 FV 内皮细胞中 CD31 和 CD34（内皮祖细胞标志物）的表达以及外周血中 CD31/CD34 细胞的比例，以评估血栓形成。分析 miR-495 对细胞活力、细胞周期和细胞凋亡的影响。IL1R1 被证实是 miR-495 的靶基因。此外，抑制 miR-495 的表达可增加 IL1R1 的表达并激活 TLR4 信号通路。FV 组织中的白细胞总数和血栓重量与长度的比值增加。过表达 miR-495 可促进 FV 内皮细胞活力。通过注射 agomiR-495 和 antagomiR-495，过表达 miR-495 的小鼠 FV 组织中的白细胞数量和血栓重量与长度的比值显著减少，IL1R1/TLR4 信号通路受到抑制。综上所述，过表达的 miR-495 直接促进 FV 内皮细胞的增殖，同时抑制其凋亡，通过抑制 TLR4 信号通路抑制 IL1R1，从而减轻 FV 血栓形成。
