Angiology and Vascular Surgery Service, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain.
Int J Mol Sci. 2020 Jun 28;21(13):4600. doi: 10.3390/ijms21134600.
microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma study (30 AAA patients, 16 healthy volunteers and 11 patients with atherosclerosis). The expression level of 179 miRNAs was screened in plasma from a subset of samples, and dysregulated miRNAs were validated in the entire study population. Dysregulated miRNAs were also quantified in aortic tissue of 21 AAA patients and 8 organ donors. Applying a gene set enrichment analysis, an interaction map of dysregulated miRNAs and their targets was built, and selected targets were quantified in tissue samples. miR-27b-3p and miR-221-3p were overexpressed in plasma of AAA patients compared with healthy controls, 1.6 times and 1.9 times, respectively. In AAA tissue, six miRNAs (miR-1, miR-27b-3p, miR-29b-3p, miR-133a-3p, miR-133b, and miR-195-5p) were underexpressed from 1.6 to 4.8 times and four miRNAs (miR-146a-5p, miR-21-5p, miR-144-3p, and miR-103a-3p) were overexpressed from 1.3 to 7.2 times. Thrombospondin-2, a target of miR-195-5p, was increased in AAA tissue and negatively correlated with the expression of miR-195-5p, suggesting their involvement in a common regulatory mechanism.
微小 RNA(miRNAs)是调节不同生物过程的小 RNA。我们的目的是鉴定在腹主动脉瘤(AAA)患者的血浆和组织中失调的 miRNAs,并探索新的潜在靶点参与 AAA。57 名患者入组进行血浆研究(30 名 AAA 患者,16 名健康志愿者和 11 名动脉粥样硬化患者)。在亚组样本中筛选了 179 个 miRNAs 的表达水平,在整个研究人群中验证了失调的 miRNAs。在 21 名 AAA 患者和 8 名器官供体的主动脉组织中也定量了失调的 miRNAs。应用基因集富集分析,构建了失调 miRNAs 及其靶基因的相互作用图,并在组织样本中定量了选定的靶基因。与健康对照组相比,AAA 患者的血浆中 miR-27b-3p 和 miR-221-3p 表达上调,分别上调 1.6 倍和 1.9 倍。在 AAA 组织中,六个 miRNAs(miR-1、miR-27b-3p、miR-29b-3p、miR-133a-3p、miR-133b 和 miR-195-5p)下调 1.6 至 4.8 倍,四个 miRNAs(miR-146a-5p、miR-21-5p、miR-144-3p 和 miR-103a-3p)上调 1.3 至 7.2 倍。miR-195-5p 的靶基因血小板反应蛋白-2在 AAA 组织中增加,并与 miR-195-5p 的表达呈负相关,提示它们参与共同的调控机制。