Department of Operating Room, The Third Xiangya Hospital, Central South University, Changsha, 410013 Hunan, China.
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013 Hunan, China.
Biomed Res Int. 2021 Jul 6;2021:9919729. doi: 10.1155/2021/9919729. eCollection 2021.
It is generally believed that excessive production of reactive oxygen species (ROS) during cardiovascular diseases impairs endothelial function. In this study, we aimed to investigate whether miR-214-3p is involved in the endothelial dysfunction induced by oxidized low-density lipoprotein (ox-LDL). In cultured vascular endothelial cells (VECs), the effects of miR-214-3p on endothelial injury induced by 100 mg/L ox-LDL were evaluated by knockdown of miR-214-3p. Western blotting was used to determine the expression of glutathione peroxidase 4 (GPX4) and endothelial nitric oxide synthase (eNOS) in VECs under different conditions. A luciferase reporter assay was used to identify GPX4 as the target of miR-214-3p. Our data showed that 100 mg/L ox-LDL significantly decreased the expression of GPX4 and eNOS, which was associated with increases in ROS levels and impairments of VEC viability and migration. Knockdown of miR-214-3p could partially reduce the increase in ROS, restore the decreased expression of GPX4 and eNOS, and thus rescue the impaired endothelial function caused by ox-LDL. Our data demonstrated that ox-LDL could induce upregulation of miR-214-3p and result in suppression of GPX4 in VECs. Downregulation of miR-214-3p could protect VECs from ROS-induced endothelial dysfunction by reversing its inhibitory effect on GPX4 expression.
人们普遍认为，心血管疾病中活性氧（ROS）的过度产生会损害内皮功能。在这项研究中，我们旨在研究 miR-214-3p 是否参与氧化型低密度脂蛋白（ox-LDL）诱导的内皮功能障碍。在培养的血管内皮细胞（VECs）中，通过 miR-214-3p 的敲低来评估 miR-214-3p 对 100mg/L ox-LDL 诱导的内皮损伤的影响。Western blot 用于确定不同条件下 VECs 中谷胱甘肽过氧化物酶 4（GPX4）和内皮型一氧化氮合酶（eNOS）的表达。荧光素酶报告基因检测用于鉴定 GPX4 是 miR-214-3p 的靶标。我们的数据表明，100mg/L ox-LDL 显著降低了 GPX4 和 eNOS 的表达，这与 ROS 水平的升高以及 VEC 活力和迁移的损伤有关。miR-214-3p 的敲低可以部分减少 ROS 的增加，恢复降低的 GPX4 和 eNOS 的表达，从而挽救 ox-LDL 引起的受损内皮功能。我们的数据表明，ox-LDL 可以诱导 miR-214-3p 的上调，并导致 VEC 中 GPX4 的抑制。miR-214-3p 的下调可以通过逆转其对 GPX4 表达的抑制作用来保护 VEC 免受 ROS 诱导的内皮功能障碍。
