Zalewski Daniel P, Ruszel Karol P, Stępniewski Andrzej, Gałkowski Dariusz, Bogucki Jacek, Komsta Łukasz, Kołodziej Przemysław, Chmiel Paulina, Zubilewicz Tomasz, Feldo Marcin, Kocki Janusz, Bogucka-Kocka Anna
Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.
Chair of Medical Genetics, Department of Clinical Genetics, Medical University of Lublin, 11 Radziwiłłowska St., 20-080 Lublin, Poland.
J Clin Med. 2020 Apr 25;9(5):1251. doi: 10.3390/jcm9051251.
Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.
慢性静脉疾病（CVD）是一种下肢血管疾病，在全球范围内具有较高的患病率。其病理特征包括静脉曲张、静脉瓣膜功能障碍以及由于细胞增殖、凋亡和血管生成功能障碍导致的皮肤溃疡。这些过程部分受微小RNA（miRNA）依赖的基因表达调控，这表明miRNA可能是CVD进展诊断和治疗中的一个重要潜在靶点。本研究的目的是分析CVD中miRNA和基因表达的变化，以及确定miRNA介导的基因表达变化及其与CVD发生发展的潜在联系。使用下一代测序技术，研究了CVD患者与健康对照者外周血单核细胞中的miRNA和基因表达谱。使用DESeq2、偏最小二乘无信息变量消除法（UVE-PLS）和ROC（受试者工作特征）方法，确定了31种miRNA和62个基因作为CVD的潜在生物标志物。预测了潜在生物标志物miRNA与基因之间的调控相互作用。对miRNA调控基因的功能分析揭示了与心血管疾病和危险因素密切相关的术语。该研究为CVD病理过程中涉及的miRNA依赖调控机制提供了新的见解。被提议作为CVD生物标志物的miRNA和基因可用于开发新的诊断和治疗方法。
