Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
J Cell Biochem. 2019 Dec;120(12):19810-19824. doi: 10.1002/jcb.29286. Epub 2019 Jul 18.
Coronary artery disease (CAD) is a multicellular disease characterized by chronic inflammation. Peripheral blood-mononuclear cells (PBMCs), as a critical component of immune system, actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in perturbed PBMC expression. STAT1 is believed to be relevant to CAD pathogenesis through regulating key inflammatory processes and modulating STAT1 expression play key roles in fine-tuning CAD-related inflammatory processes. This study evaluated PBMC expressions of STAT1, and its regulators (miR-150 and miR-223) in a cohort including 72 patients with CAD with significant ( ≥ 50%) stenosis, 30 patients with insignificant ( < 50%) coronary stenosis (ICAD), and 74 healthy controls, and assessed potential of PBMC expressions to discriminate between patients and controls. We designed quantitative real-time polymerase chain reaction (RT-qPCR) assays and identified stable reference genes for normalizing PBMC quantities of miR-150, miR-223, and STAT1 applying geNorm algorithm to six small RNAs and five mRNAs. There was no significant difference between CAD and ICAD patients regarding STAT1 expression. However, both groups of patients had higher levels of STAT1 than healthy controls. miR-150 and miR-223 were differently expressed across three groups of subjects and were downregulated in patients compared with healthy controls, with the lowest expression levels being observed in patients with ICAD. ROC curves suggested that PBMC expressions may separate between different groups of study subjects. PBMC expressions also discriminated different clinical manifestations of CAD from ICADs or healthy controls. In conclusion, the present study reported PBMC dysregulations of STAT1, miR-150, and miR-223, in patients with significant or insignificant coronary stenosis and suggested that these changes may have diagnostic implications.
冠状动脉疾病(CAD)是一种以慢性炎症为特征的多细胞疾病。外周血单核细胞(PBMC)作为免疫系统的关键组成部分,与内皮细胞损伤引起的病理生理条件积极相互作用,反映在 PBMC 表达的紊乱上。STAT1 被认为与 CAD 发病机制有关,通过调节关键的炎症过程,并调节 STAT1 的表达,在精细调节 CAD 相关炎症过程中发挥关键作用。本研究评估了包括 72 例有明显(≥50%)狭窄的 CAD 患者、30 例有不明显(<50%)冠状动脉狭窄的患者(ICAD)和 74 例健康对照者在内的队列中 PBMC 中 STAT1 及其调节因子(miR-150 和 miR-223)的表达,并评估了 PBMC 表达区分患者和对照组的潜力。我们设计了定量实时聚合酶链反应(RT-qPCR)检测,并应用 geNorm 算法对六种小 RNA 和五种 mRNA 对 PBMC 数量进行了 miR-150、miR-223 和 STAT1 的稳定参考基因的鉴定。在 CAD 和 ICAD 患者之间,STAT1 的表达没有显著差异。然而,两组患者的 STAT1 水平均高于健康对照组。miR-150 和 miR-223 在三组受试者中表达不同,且在患者中与健康对照组相比表达下调,在 ICAD 患者中表达水平最低。ROC 曲线提示 PBMC 表达可能区分不同的研究对象组别。PBMC 表达还区分了 CAD 和 ICAD 患者或健康对照组之间不同的临床表现。总之,本研究报告了在有明显或不明显冠状动脉狭窄的患者中,PBMC 中 STAT1、miR-150 和 miR-223 的失调,并提示这些变化可能具有诊断意义。