Characterization of serum miRNAs as molecular biomarkers for acute Stanford type A aortic dissection diagnosis

Zhenjun Xu,Jun Pan,Dongxia Hou,Shasha Zheng,Yunxing Xue,Xia Sheng,Hailong Cao,Zhe Wei,Qing Zhou,Qiang Wang,Dongjin Wang,Hoshun Chong,Chen-Yu Zhang,Xiaohong Jiang

doi:10.1038/s41598-017-13696-3

Abstract

Early and convenient diagnosis is urgently needed for acute Stanford type A aortic dissection (AAAD) patients due to its high mortality within the first 48 hours. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular diseases, however, little is known about circulating miRNAs involved in AAAD. Here, the blood serum was sampled from 104 AAAD+ patients and 103 age-matched donors. Initial screening was conducted using the TaqMan Low Density Array followed by RT-qPCR confirmation. According to the two-phase selection and validation process, we found that miR-25, miR-29a and miR-155 were significantly elevated, while miR-26b was markedly decreased in AAAD+ serum samples compared with AAAD− individuals. Most importantly, for individuals with hypertension, which is a major contributor to AAAD, the 4-miRNA panel also showed high accuracy in predicting those who are more likely to develop AAAD. In the blind trial set, the panel correctly classified 93.33% AAAD+ patients and 86.67% controls from the hypertension cohort. Finally, the serum miRNA-based biomarker for early AAAD detection was supported by a retrospective analysis. Taken together, we identify a distinct profile of 4-miRNA that can serve as a noninvasive biomarker for AAAD diagnosis, especially for those with hypertension.

Highlights

Aortic dissection (AD) is a catastrophe of the aorta, which is associated with high mortality[1,2,3]
25 acute Stanford type A aortic dissection (AAAD)+ cases, 30 matched AAAD− controls were subjected to ABI TaqMan Low Density array (TLDA) and RT-qPCR analysis
There was no significant difference in the distribution of age between different groups of cohorts, while the AAAD+ group had more hyperlipidemia patients and alcoholic abusers than the AAAD− control groups

Summary

Introduction

Aortic dissection (AD) is a catastrophe of the aorta, which is associated with high mortality[1,2,3]. Circulating miRNAs are have been proven to be useful biomarkers to monitor the dilation of the aneurysm[23,24] Both aortic aneurysm and AAAD are severe vascular diseases and life-threatening[1,2]. Several studies have reported that circulating miRNA expression patterns differ between aortic aneurysm patients and healthy controls, suggesting the diagnostic and therapeutic potential of miRNAs in this disease[24,25,27,28,29]. As we known that hypertension is the most important contributor of AAAD, it is necessary to know whether we can use serum miRNA as biomarkers to predict which subset of individuals trends to develop AAAD13. We obtained a profile of four serum miRNAs, which can serve as novel noninvasive biomarkers for early AAAD diagnosis

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Conclusion