College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning, 110167, China.
Department of Cardiology and Cardiovascular Research Institute, General Hospital of Northern Theater Command, 83 Wenhua Road, Shenyang, 110016, Liaoning, China.
J Mol Med (Berl). 2022 Aug;100(8):1209-1221. doi: 10.1007/s00109-022-02230-2. Epub 2022 Jul 15.
Abdominal aortic aneurysm (AAA) can be fatal if ruptured, but there is no predictive biomarker. Our aim was to evaluate the prognostic potential of microRNAs (miRNAs/miRs) in an AAA mouse model and patients with unruptured AAA (URAAA) and ruptured AAA (RAAA). Among the 64 miRNAs differentially expressed in mice with AAA compared to control, miR-30c-1-3p, miR-432-3p, miR-3154, and miR-379-5p had high homology with human miRNAs. MiR-30c-1-3p plasma levels were significantly lower in patients with RAAA than in those with URAAA or control and tended to negatively correlate with the maximum aortic diameter (r = -0.3153, P = 0.06109). MiR-30c-1-3p targeted matrix metalloproteinase (MMP)-9 mRNA through the coding region and downregulated its expression in vitro. MMP-9 plasma concentrations were significantly higher in the RAAA group than in the URAAA group (P < 0.001) and were negatively associated with miR-30c-1-3p levels (r = -0.3671, P = 0.01981) and positively-with the maximal aortic diameter (r = 0.6251, P < 0.0001). The optimal cutoff values for MMP-9 expression and the maximal aortic diameter were 461.08 ng/ml and 55.95 mm, with areas under the curve of 0.816 and 0.844, respectively. Our results indicate that plasma levels of miR-30c-1-3p and MMP-9 may be candidate biomarkers of AAA progression. KEY MESSAGES: Downregulation of miR-30c-1-3p expression and upregulation of its potential target MMP-9 are predictors of the devastation of AAA. Downregulation of miR-30c-1-3p expression and its downstream impact on MMP-9 have a potential on predicting the development and rupture of AAA.
腹主动脉瘤(AAA)如果破裂可能是致命的,但目前没有预测性的生物标志物。我们的目的是评估 microRNAs(miRNAs/miRs)在 AAA 小鼠模型和未破裂 AAA(URAAA)及破裂 AAA(RAAA)患者中的预后潜力。在与对照相比 AAA 小鼠中差异表达的 64 个 miRNAs 中,miR-30c-1-3p、miR-432-3p、miR-3154 和 miR-379-5p 与人 miRNA 具有高度同源性。与 URAAA 或对照相比,RAAA 患者的 miR-30c-1-3p 血浆水平显著降低,且与最大主动脉直径呈负相关(r = -0.3153,P = 0.06109)。miR-30c-1-3p 通过编码区靶向基质金属蛋白酶(MMP)-9mRNA 并下调其在体外的表达。与 URAAA 组相比,RAAA 组的 MMP-9 血浆浓度显著升高(P < 0.001),与 miR-30c-1-3p 水平呈负相关(r = -0.3671,P = 0.01981),与最大主动脉直径呈正相关(r = 0.6251,P < 0.0001)。MMP-9 表达和最大主动脉直径的最佳截断值分别为 461.08 ng/ml 和 55.95 mm,曲线下面积分别为 0.816 和 0.844。我们的结果表明,miR-30c-1-3p 和 MMP-9 的血浆水平可能是 AAA 进展的候选生物标志物。关键信息:miR-30c-1-3p 表达下调及其潜在靶标 MMP-9 的上调是 AAA 破坏的预测指标。miR-30c-1-3p 表达下调及其对 MMP-9 的下游影响可能有助于预测 AAA 的发生和破裂。