Department of Internal Medicine, College of Medicine, Jouf University, Sakaka, Saudi Arabia.
Mediators Inflamm. 2022 Jun 30;2022:9661940. doi: 10.1155/2022/9661940. eCollection 2022.
The purpose of this study was to explore the clinical value of altered plasma mir-21 expression level as a biomarker for the severity of coronary artery disease (CAD) and its molecular impact on HUVEC cellular injuries. Angiographically validated 56 patients with single-vessel CAD disease, 92 patients with double-vessel CAD, 139 complex coronary artery stenosis patients, and 56 healthy individuals ( = 343) were enrolled in this study. The expressions of plasma mir-21 were evidently and progressively higher while PDCD4 levels were significantly and steadily lower in single-, dual-, and multivessel occluded CAD patients than in healthy participants ( < 0.001). The relative expressions of mir-21 in hypoxia-reoxygenation- (HR-) exposed HUVECs were markedly upregulated, but PDCD4 concentrations were obviously downregulated as compared with normal control cells ( < 0.001). Moreover, altered circulatory mir-21 expression levels were able to significantly differentiate single- (AUC 0.893), double- (AUC 0.914), and multivessel stenosis CAD (AUC 0.933) patients from healthy subjects. Besides, the plasma mir-21 expressions in elderly (66-85 years) groups were remarkably higher than those in younger aged (25-45 years) subjects. Caspase-3 and ROS expression levels were remarkably elevated, but cellular viability noticeably declined in HR-induced HUVECs than in normoxic cells ( < 0.001). In contrast, mir-21 inhibition markedly reduced caspase-3 activity and ROS concentrations while significantly ameliorating HUVEC cellular viability in HR conditions. PDCD4 expressions in HR-exposed HUVECs were prominently decreased whereas mir-21 inhibition significantly enhanced PDCD4 levels ( < 0.001). Upregulated plasma mir-21 can be a valuable clinical biomarker for the detection of the severity of coronary artery stenosis patients. Elevated circulatory mir-21 concentrations have a positive correlation with aging. Inhibitory mir-21 evidently increased HUVEC cellular viability through upregulation of targeting PDCD4 and recommended a newer possible therapeutic molecule for the management of CAD patients.
本研究旨在探讨改变的血浆 mir-21 表达水平作为冠状动脉疾病 (CAD) 严重程度的生物标志物的临床价值及其对 HUVEC 细胞损伤的分子影响。本研究纳入了 56 例单支血管 CAD 患者、92 例双支血管 CAD 患者、139 例复杂冠状动脉狭窄患者和 56 例健康个体 (共 343 例)。与健康参与者相比，单支、双支和多支闭塞 CAD 患者的血浆 mir-21 表达明显且逐渐升高，而 PDCD4 水平则明显且稳定降低 ( < 0.001)。与正常对照细胞相比，缺氧再复氧 (HR) 暴露的 HUVEC 中 mir-21 的相对表达明显上调，而 PDCD4 浓度明显下调 ( < 0.001)。此外，改变的循环 mir-21 表达水平能够显著区分单支 (AUC 0.893)、双支 (AUC 0.914) 和多支狭窄 CAD 患者与健康受试者。此外，老年 (66-85 岁) 组的血浆 mir-21 表达明显高于年轻组 (25-45 岁)。HR 诱导的 HUVEC 中 caspase-3 和 ROS 表达水平明显升高，而细胞活力明显下降 ( < 0.001)。相反，mir-21 抑制显著降低 caspase-3 活性和 ROS 浓度，同时显著改善 HR 条件下 HUVEC 的细胞活力。HR 暴露的 HUVEC 中 PDCD4 的表达明显降低，而 mir-21 抑制显著增加 PDCD4 水平 ( < 0.001)。上调的血浆 mir-21 可作为检测冠状动脉狭窄患者严重程度的有价值的临床生物标志物。循环中 mir-21 浓度的升高与年龄增长呈正相关。抑制 mir-21 通过上调靶标 PDCD4 明显增加 HUVEC 细胞活力，为 CAD 患者的治疗提供了一种新的潜在治疗分子。
