Kawasaki disease (KD) causes cardiovascular system injury in children. However, the pathogenic mechanisms of KD have not been well defined. Recently, strong correlation between aberrant microRNAs and KD nosogenesis has been revealed. A role of microRNA-197-3p (miR-197-3p) in the pathogenesis of KD is identified in the present study. Cell proliferation assay showed human coronary artery endothelial cells (HCAECs) were suppressed by serum from KD patients, which was correlated with high levels of miR-197-3p in both KD serum and HCAECs cultured with KD serum. The inhibition of HCAECs by miR-197-3p was confirmed by cells expressing miR-197-3p mimic and miR-197-3p inhibitor. Comparative proteomics analysis and Ingenuity Pathway Analysis (IPA) revealed TIMP3 as a potential target of miR-197-3p, which was demonstrated by western blot and dual-luciferase reporter assays. Subsequently, by detecting the endothelium damage markers THBS1, VWF, and HSPG2, the role of miR-197-3p/TIMP3 in KD-induced damage to HCAECs was confirmed, which was further validated by a KD mouse model in vivo. The expressions of miR-197-3p and its target, TIMP3, are dramatically variational in KD serum and HCAECs cultured with KD serum. Increased miR-197-3p induces HCAECs abnormal by restraining TIMP3 expression directly. Hence, dysregulation of miR-197-3p/TIMP3 expression in HCAECs may be an important mechanism in cardiovascular endothelium injury in KD patients, which offers a feasible therapeutic target for KD treatment.

川崎病 (KD) 会导致儿童心血管系统损伤。然而，KD的发病机制尚未明确。最近，已经揭示了异常 microRNA 与 KD 发病之间的强相关性。本研究确定了 microRNA-197-3p (miR-197-3p) 在 KD 发病机制中的作用。细胞增殖试验显示，KD 患者的血清抑制了人冠状动脉内皮细胞 (HCAECs)，这与 KD 血清和用 KD 血清培养的 HCAECs 中的高水平 miR-197-3p 相关。表达 miR-197-3p 模拟物和 miR-197-3p 抑制剂的细胞证实了 miR-197-3p 对 HCAEC 的抑制作用。比较蛋白质组学分析和 Ingenuity Pathway Analysis (IPA) 揭示了 TIMP3 作为 miR-197-3p 的潜在靶标，这通过蛋白质印迹和双荧光素酶报告基因测定得到证实。随后，通过检测内皮损伤标志物THBS1、VWF和HSPG2，证实了miR-197-3p/TIMP3在KD诱导的HCAECs损伤中的作用，并通过体内KD小鼠模型进一步验证。miR-197-3p 及其靶点 TIMP3 的表达在 KD 血清和用 KD 血清培养的 HCAECs 中存在显着差异。增加的 miR-197-3p 通过直接抑制 TIMP3 表达来诱导 HCAECs 异常。因此，HCAECs中miR-197-3p/TIMP3表达失调可能是KD患者心血管内皮损伤的重要机制，为KD治疗提供了一个可行的治疗靶点。证实了 miR-197-3p/TIMP3 在 KD 诱导的 HCAECs 损伤中的作用，并通过体内 KD 小鼠模型进一步验证。miR-197-3p 及其靶点 TIMP3 的表达在 KD 血清和用 KD 血清培养的 HCAECs 中存在显着差异。增加的 miR-197-3p 通过直接抑制 TIMP3 表达来诱导 HCAECs 异常。因此，HCAECs中miR-197-3p/TIMP3表达失调可能是KD患者心血管内皮损伤的重要机制，为KD治疗提供了一个可行的治疗靶点。证实了 miR-197-3p/TIMP3 在 KD 诱导的 HCAECs 损伤中的作用，并通过体内 KD 小鼠模型进一步验证。miR-197-3p 及其靶点 TIMP3 的表达在 KD 血清和用 KD 血清培养的 HCAECs 中存在显着差异。增加的 miR-197-3p 通过直接抑制 TIMP3 表达来诱导 HCAECs 异常。因此，HCAECs中miR-197-3p/TIMP3表达失调可能是KD患者心血管内皮损伤的重要机制，为KD治疗提供了一个可行的治疗靶点。