Girdauskas Evaldas, Neumann Niklas, Petersen Johannes, Sequeira-Gross Tatiana, Naito Shiho, von Stumm Maria, von Kodolitsch Yskert, Reichenspurner Hermann, Zeller Tanja
Department of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, 20246 Hamburg, Germany.
German Center of Cardiovascular Research (DZHK), Partner site Hamburg/Lübeck/Kiel, 20246 Hamburg, Germany.
J Clin Med. 2020 Jan 19;9(1):276. doi: 10.3390/jcm9010276.
Aortic size-based criteria are of limited value in the prediction of aortic events, while most aortic events occur in patients with proximal aortic diameters < 50 mm. Serological biomarkers and especially circulating microRNAs (miRNAs) have been proposed as an elegant tool to improve risk stratification in patients with different aortopathies. Therefore, we aimed to evaluate the levels of circulating miRNAs in a surgical cohort of patients presenting with bicuspid aortic valve disease and distinct valvulo-aortic phenotypes.
We prospectively examined a consecutive cohort of 145 patients referred for aortic valve surgery: (1) Sixty three patients (mean age 47 ± 11 years, 92% male) with bicuspid aortic valve regurgitation and root dilatation (BAV-AR), (2) thirty two patients (mean age 59 ± 11 years, 73% male) with bicuspid aortic valve stenosis (BAV-AS), and (3) fifty patients (mean age 56 ± 14 years, 55% male) with tricuspid aortic valve stenosis and normal aortic root diameters (TAV-AS) who underwent aortic valve+/-proximal aortic surgery at a single institution. MicroRNAs analysis included 11 miRNAs, all published previously in association with aortopathies. Endpoints of our study were (1) correlation between circulating miRNAs and aortic diameter and (2) comparison of circulating miRNAs in distinct valvulo-aortic phenotypes.
We found a significant inverse linear correlation between circulating miRNAs levels and proximal aortic diameter in the whole study cohort. The strongest correlation was found for miR-17 ( = -0.42, < 0.001), miR-20a ( = -0.37, < 0.001), and miR-106a ( = -0.32, < 0.001). All miRNAs were significantly downregulated in BAV vs. TAV with normal aortic root dimensions Conclusions: Our data demonstrate a significant inverse correlation between circulating miRNAs levels and the maximal aortic diameter in BAV aortopathy. When comparing miRNAs expression patterns in BAV vs. TAV patients with normal aortic root dimensions, BAV patients showed significant downregulation of analyzed miRNAs as compared to their TAV counterparts. Further multicenter studies in larger cohorts are needed to further validate these results.
基于主动脉大小的标准在预测主动脉事件方面价值有限，而大多数主动脉事件发生在近端主动脉直径<50mm的患者中。血清生物标志物，尤其是循环微小RNA（miRNA），已被提议作为一种优化的工具，用于改善不同主动脉病变患者的风险分层。因此，我们旨在评估一组接受手术治疗的二叶式主动脉瓣疾病及不同瓣膜-主动脉表型患者的循环miRNA水平。
我们前瞻性地研究了连续145例因主动脉瓣手术而转诊的患者队列：（1）63例（平均年龄47±11岁，92%为男性）患有二叶式主动脉瓣反流及根部扩张（BAV-AR）的患者，（2）32例（平均年龄59±11岁，73%为男性）患有二叶式主动脉瓣狭窄（BAV-AS）的患者，以及（3）50例（平均年龄56±14岁，55%为男性）患有三尖瓣主动脉瓣狭窄且主动脉根部直径正常（TAV-AS）的患者，这些患者均在同一机构接受了主动脉瓣+/-近端主动脉手术。miRNA分析包括11种miRNA，所有这些miRNA此前均已发表，且与主动脉病变相关。我们研究的终点为：（1）循环miRNA与主动脉直径之间的相关性，以及（（2）不同瓣膜-主动脉表型中循环miRNA的比较。
我们在整个研究队列中发现循环miRNA水平与近端主动脉直径之间存在显著的负线性相关性。miR-17（r=-0.42，P<0.001）、miR-20a（r=-0.37，P<0.001）和miR-106a（r=-0.32，P<0.001）的相关性最强。在主动脉根部尺寸正常的情况下，与三尖瓣主动脉瓣（TAV）相比，二叶式主动脉瓣（BAV）中的所有miRNA均显著下调。结论：我们的数据表明，在BAV主动脉病变中，循环miRNA水平与最大主动脉直径之间存在显著的负相关性。在比较主动脉根部尺寸正常的BAV患者与TAV患者的miRNA表达模式时，BAV患者与TAV患者相比，所分析的miRNA显著下调。需要在更大的队列中进行进一步的多中心研究，以进一步验证这些结果。
