Department of Internal Medicine, Angiology and Coagulation Unit, University Hospital of Parma, Parma, Italy.
Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy.
Semin Thromb Hemost. 2021 Nov;47(8):982-991. doi: 10.1055/s-0041-1726341. Epub 2021 Jul 9.
Venous thromboembolism (VTE) is the third most common cardiovascular disease. Interleukins (ILs) and micro-ribonucleic acids (miRNAs) have been proposed as molecules able to modulate endothelial inflammation and platelet hyperactivity. At present, no early biomarkers are available to predict the outcome of VTE. We investigated in a pilot study a selected number of miRNAs and ILs as prognostic VTE biomarkers and reviewed literature in this setting. Twenty-three patients (aged 18-65) with a new diagnosis of non-oncological VTE and free from chronic inflammatory diseases were enrolled. Twenty-three age- and sex-matched healthy blood donors were evaluated as control subjects. Serum miRNAs (MiRNA 126, 155, 17.92, 195), inflammatory cytokines (IL-6, tumor necrosis factor-α, IL-8), and lymphocyte subsets were evaluated in patients at enrolment (T0) and in controls. In VTE patients, clinical and instrumental follow-up were performed assessing residual vein obstruction, miRNA and ILs evaluation at 3 months' follow-up (T1). At T0, IL-8, activated T lymphocytes, Treg lymphocytes, and monocytes were higher in patients compared with healthy controls, as were miRNA 126 levels. Moreover, miRNA 126 and IL-6 were significantly increased at T0 compared with T1 evaluation in VTE patients. Higher levels of MiR126 at T0 correlated with a significant overall thrombotic residual at follow-up. In recent years an increasing number of studies (case-control studies, in vivo studies in animal models, in vitro studies) have suggested the potential role of miRNAs in modulating the cellular and biohumoral responses involved in VTE. In the frame of epidemiological evidence, this pilot study with a novel observational approach supports the notion that miRNA can be diagnostic biomarkers of VTE and first identifies miRNA 126 as a predictor of outcome, being associated with poor early recanalization.
静脉血栓栓塞症（VTE）是第三大常见心血管疾病。白细胞介素（ILs）和微小 RNA（miRNAs）已被提出作为能够调节内皮炎症和血小板高反应性的分子。目前，尚无可用于预测 VTE 结局的早期生物标志物。我们在一项初步研究中研究了选定数量的 miRNAs 和 ILs 作为预测 VTE 的生物标志物，并在此背景下回顾了文献。共纳入 23 例新诊断的非肿瘤性 VTE 且无慢性炎症性疾病的患者。23 名年龄和性别匹配的健康献血者作为对照进行评估。在患者入组时（T0）和对照组评估血清 miRNAs（miRNA 126、155、17.92、195）、炎症细胞因子（IL-6、肿瘤坏死因子-α、IL-8）和淋巴细胞亚群。在 VTE 患者中，进行临床和仪器随访，评估残留静脉阻塞，并在 3 个月随访时（T1）评估 miRNA 和 ILs。在 T0 时，与健康对照组相比，患者的 IL-8、活化 T 淋巴细胞、Treg 淋巴细胞和单核细胞更高，miRNA 126 水平也更高。此外，与 VTE 患者的 T1 评估相比，miRNA 126 和 IL-6 在 T0 时显著增加。T0 时较高的 MiR126 水平与随访时明显的总体血栓残留相关。近年来，越来越多的研究（病例对照研究、动物模型体内研究、体外研究）表明 miRNAs 在调节与 VTE 相关的细胞和生物体液反应方面具有潜在作用。在流行病学证据的框架内，这项具有新的观察方法的初步研究支持了 miRNA 可以作为 VTE 的诊断生物标志物的观点，并首次确定 miRNA 126 是预后的预测因子，与早期再通不良相关。
