Sun Limin, He Xin, Zhang Tao, Tao Guizhou, Wang Xin
Department of General Practice, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Front Cardiovasc Med. 2021 Sep 3;8:701058. doi: 10.3389/fcvm.2021.701058. eCollection 2021.
Atherosclerosis is a major cause of coronary artery disease (CAD), and CAD is one of the main causes leading to death in most countries. It has been reported that lncRNAs play important roles in the development of atherosclerosis; thus, we aimed to explore lncRNAs that are closely related to the occurrence and development of atherosclerosis. The data GSE113079 from the GEO database was used to explore the dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) between 93 patients with CAD and 48 healthy controls. Next, RT-qPCR was performed to detect the level of lncRNAs in HUVEC cells and CCK-8 was performed to detect cell viability. Then, flow cytometry assays were used to determine the apoptosis of HUVEC. In addition, ELISA assay was used to measure the concentrations of triglyceride (TG), low density lipoprotein cholesterin (LDL-C), and high density lipoprotein cholesterol (HDL-C). Moreover, western blot assay was used to detect the expression of proteins. lnc-KCNC3-3:1 was significantly upregulated in PBMCs of patients with CAD. In addition, oxidized low density lipoprotein (oxLDL) notably inhibited the proliferation and induced the apoptosis of HUVEC, while this phenomenon was notably reversed by lnc-KCNC3-3:1 knockdown. Moreover, oxLDL significantly promoted the migration of HUVECs, which was significantly restored by knockdown of lnc-KCNC3-3:1. Moreover, lnc-KCNC3-3:1 siRNA1 could reverse oxLDL-induced HUVEC growth inhibition, and lnc-KCNC3-3:1 silencing could inhibit the expressions of p-JAK1 and p-STAT3 in oxLDL-treated HUVECs. Animal study revealed that knockdown of lnc-KCNC3-3:1 alleviated the symptom of atherosclerosis, and it could inhibit the expressions of p-JAK1, p-STAT3 and p-Akt in tissues of atherosclerosis mice. Knockdown of lnc-KCNC3-3:1 alleviates the development of atherosclerosis via downregulation of JAK1/STAT3 signaling pathway. These data indicated that lnc-KCNC3-3:1 might serve as a potential target for the treatment of atherosclerosis.
动脉粥样硬化是冠心病（CAD）的主要病因，而CAD是大多数国家导致死亡的主要原因之一。据报道，长链非编码RNA（lncRNAs）在动脉粥样硬化的发展中起重要作用；因此，我们旨在探索与动脉粥样硬化发生发展密切相关的lncRNAs。利用来自基因表达综合数据库（GEO数据库）的数据GSE113079，探索93例CAD患者和48例健康对照者外周血单个核细胞（PBMCs）中失调的lncRNAs。接下来，进行逆转录定量聚合酶链反应（RT-qPCR）检测人脐静脉内皮细胞（HUVEC）中lncRNAs的水平，并进行细胞计数试剂盒-8（CCK-8）检测细胞活力。然后，采用流式细胞术检测HUVEC的凋亡情况。此外，酶联免疫吸附测定（ELISA）法用于检测甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）的浓度。此外，蛋白质免疫印迹法用于检测蛋白质的表达。lnc-KCNC3-3:1在CAD患者的PBMCs中显著上调。此外，氧化型低密度脂蛋白（oxLDL）显著抑制HUVEC的增殖并诱导其凋亡，而lnc-KCNC3-3:1敲低可显著逆转这一现象。此外，oxLDL显著促进HUVEC的迁移，lnc-KCNC3-3:1敲低可使其显著恢复。此外，lnc-KCNC3-3:1小干扰RNA1（siRNA1）可逆转oxLDL诱导的HUVEC生长抑制，lnc-KCNC3-3:1沉默可抑制oxLDL处理的HUVEC中磷酸化JAK1（p-JAK1）和磷酸化信号转导子和转录激活子3（p-STAT3）的表达。动物研究表明，lnc-KCNC3-3:1敲低可减轻动脉粥样硬化症状，并可抑制动脉粥样硬化小鼠组织中p-JAK1、p-STAT3和磷酸化蛋白激酶B（p-Akt）的表达。lnc-KCNC3-3:1敲低通过下调JAK1/STAT3信号通路减轻动脉粥样硬化的发展。这些数据表明，lnc-KCNC3-3:1可能是治疗动脉粥样硬化的潜在靶点。
