Li Wei, Li Yi, Zhi Wei, Liu Chen, Fan Weize, Miao Qing, Gu Xinshun
Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
Exp Ther Med. 2021 Dec;22(6):1437. doi: 10.3892/etm.2021.10872. Epub 2021 Oct 12.
Acute coronary syndrome (ACS) is the main manifestation of cardiovascular disease and the primary cause of adult hospitalization in China. There is an urgent demand for novel biomarkers for the diagnosis of ACS. Although plasma cysteine-rich protein 61 (Cyr61) has been previously reported to be accurate for ACS diagnosis, the accuracy of exosomal Cyr61 in ACS diagnosis remains unknown. In the present study, the aim was to assess the potential of applying exosomal Cyr61 in ACS diagnosis and to explore the role of Cyr61 in vascular remodeling . The abundance of Cyr61 in plasma-derived exosomes from patients with unstable angina pectoris (UAP), acute myocardial infarction (AMI) patients in addition to those isolated from healthy individuals were detected using an ELISA kit. The association between exosomal Cyr61 levels and clinical characteristics of ACS patients was analyzed through χ test, Fisher's exact test and Student's t-test. Receiver operating characteristic (ROC) curve analysis was used to determine the accuracy of using exosomal Cyr61 as a biomarker of ACS diagnosis. Furthermore, independent predictors of the existence of ACS were investigated through a multivariate analysis. Subsequently, the role of Cyr61 on vascular remodeling was evaluated in vascular smooth muscle cells (VSMCs) upon oxidized low-density lipoprotein (ox-LDL) treatment by performing Cyr61 knockdown, Cell Counting Kit-8, flow cytometry and Transwell assays. Exosomal Cyr61 expression was found to be significantly elevated in patients with ACS compared with that in healthy individuals. In addition, exosomal Cyr61 levels were associated with sex, family history of ACS and glucose levels. ROC curve analyzes revealed that exosomal Cyr61 expression could be used to differentiate patients with UAP, AMI and ACS from healthy individuals. Furthermore, exosomal Cyr61 levels were independently correlated with the existence of ACS. , Cyr61 expression was demonstrated to be significantly increased in VSMCs after ox-LDL exposure in a concentration- and time-dependent manner. Functionally, the elevated cell viability and migration of VSMCs induced by ox-LDL were partially but significantly inhibited by Cyr61 knockdown. By contrast, knocking down Cyr61 expression significantly elevated the apoptosis rate of VSMCs compared with that in the ox-LDL-treated group. In conclusion, data from the present study suggest that Cyr61 serve a regulatory role in vascular remodeling , where exosomal Cyr61 levels may represent a promising biomarker for ACS diagnosis.
急性冠状动脉综合征（ACS）是心血管疾病的主要表现形式，也是中国成年人住院的主要原因。对于用于诊断ACS的新型生物标志物有着迫切需求。尽管此前已有报道称血浆富含半胱氨酸蛋白61（Cyr61）对ACS诊断准确，但外泌体Cyr61在ACS诊断中的准确性仍不清楚。在本研究中，目的是评估应用外泌体Cyr61进行ACS诊断的潜力，并探索Cyr61在血管重塑中的作用。使用酶联免疫吸附测定试剂盒检测不稳定型心绞痛（UAP）患者、急性心肌梗死（AMI）患者以及健康个体血浆来源外泌体中Cyr61的丰度。通过χ检验、Fisher精确检验和学生t检验分析外泌体Cyr61水平与ACS患者临床特征之间的关联。采用受试者工作特征（ROC）曲线分析来确定使用外泌体Cyr61作为ACS诊断生物标志物的准确性。此外，通过多变量分析研究ACS存在的独立预测因素。随后，通过进行Cyr61敲低、细胞计数试剂盒8、流式细胞术和Transwell分析，评估Cyr61在氧化型低密度脂蛋白（ox-LDL）处理的血管平滑肌细胞（VSMC）中对血管重塑的作用。发现ACS患者外泌体Cyr61表达与健康个体相比显著升高。此外，外泌体Cyr61水平与性别、ACS家族史和血糖水平相关。ROC曲线分析显示，外泌体Cyr61表达可用于区分UAP、AMI和ACS患者与健康个体。此外，外泌体Cyr61水平与ACS的存在独立相关。而且，在ox-LDL暴露后，VSMC中Cyr61表达呈浓度和时间依赖性显著增加。在功能上，ox-LDL诱导的VSMC细胞活力和迁移升高被Cyr61敲低部分但显著抑制。相比之下，与ox-LDL处理组相比，敲低Cyr61表达显著提高了VSMC的凋亡率。总之，本研究数据表明Cyr61在血管重塑中起调节作用，其中外泌体Cyr61水平可能代表ACS诊断的一个有前景的生物标志物。
