Zalewski Daniel, Chmiel Paulina, Kołodziej Przemysław, Feldo Marcin, Stępniewski Andrzej, Ziaja-Sołtys Marta, Łuszczak Joanna, Stanek Agata, Kocki Janusz, Bogucka-Kocka Anna
Chair and Department of Biology and Genetics, Medical University of Lublin, 4a Chodźki St., 20-093 Lublin, Poland.
Randox Laboratories Ltd., Poznańska St., 00-680 Warszawa, Poland.
Int J Mol Sci. 2025 Sep 9;26(18):8786. doi: 10.3390/ijms26188786.
Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and varicose veins (VV) are frequently underdiagnosed and undertreated peripheral vascular diseases that pose considerable public health challenges. More research is required to elucidate the pathophysiological mechanisms underlying these conditions and to identify novel diagnostic and therapeutic biomarkers. Therefore, in our study, we aimed to identify shared and distinct pathways associated with angiogenesis and inflammation in LEAD, AAA, and VV. The expression of 18 genes in peripheral blood mononuclear cells and the plasma levels of six proteins were compared between groups of 40 patients with LEAD, 40 patients with AAA, and 40 patients with VV. Independent RNA-seq and microRNA-seq data were integrated to predict differentially expressed transcription factors and microRNAs associated with the most significant genes. Gene Ontology functional analysis was performed to determine the potential biological effects of the observed dysregulations. The elevated expression of and , along with increased plasma levels of VEGF-C and reduced plasma levels of VEGF-A, were distinguishing features of patients with LEAD compared to those with AAA and VV. Decreased plasma levels of TGF-alpha and TGF-beta 1 were found to be indicative of varicose veins compared to individuals with arterial diseases (LEAD and AAA). Transcription factors and microRNAs potentially regulating the obtained signatures were identified and integrated into a hypothetical regulatory network. The observed dysregulations were found to be functionally associated with the response to hypoxia, the positive regulation of angiogenesis, chemotaxis, vascular permeability, and cell adhesion. The presented study identified dysregulations of key angiogenesis- and inflammation-related factors in peripheral blood mononuclear cells and plasma between LEAD, AAA, and VV patients, providing new insights into the shared and distinct molecular mechanisms underlying these diseases.
下肢动脉疾病（LEAD）、腹主动脉瘤（AAA）和静脉曲张（VV）是常见的诊断不足和治疗不足的外周血管疾病，对公共卫生构成了重大挑战。需要更多的研究来阐明这些疾病的病理生理机制，并识别新的诊断和治疗生物标志物。因此，在我们的研究中，我们旨在确定与LEAD、AAA和VV中血管生成和炎症相关的共同和独特途径。比较了40例LEAD患者、40例AAA患者和40例VV患者外周血单个核细胞中18个基因的表达以及6种蛋白质的血浆水平。整合独立的RNA测序和微小RNA测序数据，以预测与最显著基因相关的差异表达转录因子和微小RNA。进行基因本体功能分析，以确定观察到的失调的潜在生物学效应。与AAA和VV患者相比，LEAD患者中 和 的表达升高，以及VEGF-C血浆水平升高和VEGF-A血浆水平降低是其显著特征。与患有动脉疾病（LEAD和AAA）的个体相比，发现TGF-α和TGF-β1的血浆水平降低表明患有静脉曲张。确定了可能调节所获得特征的转录因子和微小RNA，并将其整合到一个假设的调控网络中。观察到的失调在功能上与对缺氧的反应、血管生成的正调控、趋化性、血管通透性和细胞粘附相关。本研究确定了LEAD、AAA和VV患者外周血单个核细胞和血浆中关键血管生成和炎症相关因子的失调，为这些疾病潜在的共同和独特分子机制提供了新的见解。
