Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Anesthesiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
J Cell Mol Med. 2021 Aug;25(16):8028-8038. doi: 10.1111/jcmm.16734. Epub 2021 Jun 25.
Atherosclerosis can result in multiple cardiovascular diseases. Circular RNAs (CircRNAs) have been reported as significant non-coding RNAs in atherosclerosis progression. Dysfunction of vascular smooth muscle cells (VSMCs) is involved in atherosclerosis. However, up to now, the effect of circ_0002984 in atherosclerosis is still unknown. Currently, we aimed to investigate the function of circ_0002984 in VSMCs incubated by oxidized low-density lipoprotein (ox-LDL). Firstly, our findings indicated that the expression levels of circ_0002984 were significantly up-regulated in the serum of atherosclerosis patients and ox-LDL-incubated VSMCs. Loss of circ_0002984 suppressed VSMC viability, cell cycle distribution and migration capacity. Then, we carried out ELISA assay to determine TNF-α and IL-6 levels. The data implied that lack of circ_0002984 obviously repressed ox-LDL-stimulated VSMC inflammation. Meanwhile, miR-326-3p, which was predicted as a target of circ_0002984, was obviously down-regulated in VSMCs treated by ox-LDL. Additionally, after overexpression circ_0002984 in VSMCs, a decrease in miR-326-3p was observed. Subsequently, miR-326-3p was demonstrated to target vesicle-associated membrane protein 3 (VAMP3). Therefore, we hypothesized that circ_0002984 could modulate expression of VAMP3 through sponging miR-326-3p. Furthermore, we confirmed that up-regulation of miR-326-3p rescued the circ_0002984 overexpressing-mediated effects on VMSC viability, migration and inflammation. Additionally, miR-326-3p inhibitor-mediated functions on VSMCs were reversed by knockdown of VAMP3. In conclusion, circ_0002984 mediated cell proliferation, migration and inflammation through modulating miR-326-3p and VAMP3 in VSMCs, which suggested that circ_0002984 might hold great promise as a therapeutic strategy for atherosclerosis.
动脉粥样硬化可导致多种心血管疾病。环状 RNA（CircRNAs）已被报道为动脉粥样硬化进展中的重要非编码 RNA。血管平滑肌细胞（VSMCs）功能障碍与动脉粥样硬化有关。然而，到目前为止，circ_0002984 在动脉粥样硬化中的作用尚不清楚。目前，我们旨在研究 circ_0002984 在氧化低密度脂蛋白（ox-LDL）孵育的 VSMCs 中的功能。首先，我们的研究结果表明，动脉粥样硬化患者血清和 ox-LDL 孵育的 VSMCs 中 circ_0002984 的表达水平显著上调。circ_0002984 的缺失抑制了 VSMC 的活力、细胞周期分布和迁移能力。然后，我们进行了 ELISA 测定来确定 TNF-α 和 IL-6 水平。数据表明，缺乏 circ_0002984 明显抑制了 ox-LDL 刺激的 VSMC 炎症。同时，miR-326-3p 作为 circ_0002984 的靶标，在 ox-LDL 处理的 VSMCs 中明显下调。此外，在 VSMCs 中转染 circ_0002984 后，观察到 miR-326-3p 减少。随后，miR-326-3p 被证明靶向囊泡相关膜蛋白 3（VAMP3）。因此，我们假设 circ_0002984 可以通过海绵吸附 miR-326-3p 来调节 VAMP3 的表达。此外，我们证实上调 miR-326-3p 可挽救 circ_0002984 过表达对 VMSC 活力、迁移和炎症的影响。此外，通过敲低 VAMP3 逆转了 miR-326-3p 抑制剂对 VSMCs 的作用。总之，circ_0002984 通过调节 VSMCs 中的 miR-326-3p 和 VAMP3 介导细胞增殖、迁移和炎症，表明 circ_0002984 可能作为动脉粥样硬化的一种有前途的治疗策略。
