Winski Greg, Chernogubova Ekaterina, Busch Albert, Eken Suzanne M, Jin Hong, Lindquist Liljeqvist Moritz, Khan Tooba, Bäcklund Alexandra, Paloschi Valentina, Roy Joy, Hultgren Rebecka, Brostjan Christine, de Borst Gert J, Sluijter Joost P G, Sachs Nadja, Eckstein Hans-Henning, Boon Reinier A, Spin Joshua M, Tsao Philip S, Asselbergs Folkert W, Maegdefessel Lars
Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
Commun Med (Lond). 2025 Jun 6;5(1):218. doi: 10.1038/s43856-025-00892-w.
MicroRNAs are post transcriptional modulators of gene expression. We explored the diagnostic and prognostic value of circulating microRNAs in abdominal aortic aneurysm (AAA) disease, for which currently no established circulating biomarker is available.
We profiled the expression of 754 human microRNAs in plasma from 187 patients with AAA and 190 matched non-diseased controls. To validate, we used two additional AAA patient cohorts, looking at circulating and aortic tissue-derived microRNA expression, and their correlation to AAA disease phenotype, as well as two murine AAA models.
We show that among 12 differentially expressed microRNAs, miR-15a and -659 are the most significantly up-regulated in AAA, whereas miR-1183 and -192 are the most significantly down-regulated. miR-15a is upregulated AAA patient tissues, and in plasma from two murine AAA models. In patients from three different cohorts, miR-15a expression levels in plasma, serum and aortic tunica media are significantly correlated with AAA diameter. Through modulation of miR-15a in human aortic smooth muscle cells, we identify several potential target genes of miR-15a known to be down-regulated in human AAA, suggesting its potential involvement in AAA pathology. Inhibition of miR-15a in vivo demonstrates a significant inhibition of murine aortic diameter growth at day 7.
Our findings suggest that miR-15a is a potential biomarker of AAA. Through in vivo studies and based on its target profile, we show that miR-15a is involved in AAA pathogenesis and could help treatment, but also assist in risk-stratification of AAA patients and identify candidates for early AAA repair.
微小RNA是基因表达的转录后调节因子。我们探讨了循环微小RNA在腹主动脉瘤（AAA）疾病中的诊断和预后价值，目前尚无已确立的循环生物标志物可用于该疾病。
我们分析了187例AAA患者和190例匹配的非患病对照者血浆中754种人类微小RNA的表达。为进行验证，我们使用了另外两个AAA患者队列，观察循环和主动脉组织来源的微小RNA表达及其与AAA疾病表型的相关性，以及两个小鼠AAA模型。
我们发现，在12种差异表达的微小RNA中，miR-15a和-659在AAA中上调最为显著，而miR-1183和-192下调最为显著。miR-15a在AAA患者组织以及来自两个小鼠AAA模型的血浆中上调。在来自三个不同队列的患者中，血浆、血清和主动脉中膜的miR-15a表达水平与AAA直径显著相关。通过调节人主动脉平滑肌细胞中的miR-15a，我们鉴定出了几种已知在人AAA中下调的miR-15a潜在靶基因，提示其可能参与AAA病理过程。体内抑制miR-15a可在第7天显著抑制小鼠主动脉直径的生长。
我们的研究结果表明，miR-15a是AAA的潜在生物标志物。通过体内研究并基于其靶标谱，我们表明miR-15a参与AAA发病机制，有助于治疗，还可协助对AAA患者进行风险分层，并识别早期AAA修复的候选者。
