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

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.

MiR-26b Suppresses the Development of Stanford Type A Aortic Dissection by Regulating HMGA2 and TGF-β/Smad3 Signaling Pathway

“…24) Also, miR-26b was discovered to participate in the pathophysiology of many cardiovascular diseases, which can improve myocardial remodeling in myocardial infarction. 25) It is the first time Xu et al 12) found that miR-26b was down-regulated in TAAD.…”

“…11) Moreover, Xu et al displayed that miR-26b was significantly decreased in TAAD and served as a biomarker for TAAD diagnosis, which might provide a new potential therapeutic target for TAAD. 12) Therefore, further understanding the molecular mechanism of miR-26b in the pathogenesis of TAAD is very essential.…”

The regulatory role of microRNAs in angiogenesis‐related diseases

“…Fortunately, emerging circulating miRNAs have been proven as effective and novel non‐invasive biomarkers for the diagnosis of early AAD. A recent study showed that the serum levels of miR‐25, miR‐29a and miR‐155 are up‐regulated, whereas miR‐26b is down‐regulated in Stanford type A aortic dissection (AAAD) patients compared with controls 204. Moreover, in AD patients tissues, Liao et al demonstrated that miR‐553, miR‐183‐3p, miR‐419‐3p, miR‐338‐5p, miR‐433 and miR‐30c are increased in the aortic tissue of thoracic aortic dissection (TAD) patients, but miR‐24, miR‐93, miR‐768‐5p, miR‐143, miR‐145, miR‐22 and miR‐26b are significantly down‐regulated,205 in which the change of miR‐26b was consistent with the serum levels 204.…”

“…A recent study showed that the serum levels of miR‐25, miR‐29a and miR‐155 are up‐regulated, whereas miR‐26b is down‐regulated in Stanford type A aortic dissection (AAAD) patients compared with controls 204. Moreover, in AD patients tissues, Liao et al demonstrated that miR‐553, miR‐183‐3p, miR‐419‐3p, miR‐338‐5p, miR‐433 and miR‐30c are increased in the aortic tissue of thoracic aortic dissection (TAD) patients, but miR‐24, miR‐93, miR‐768‐5p, miR‐143, miR‐145, miR‐22 and miR‐26b are significantly down‐regulated,205 in which the change of miR‐26b was consistent with the serum levels 204. Functionally, up‐regulated level of miR‐29 can enhance the degradation of extracellular matrix, and reduced level of miR‐143 and miR‐145 can facilitate normal contractile and quiescent VSMCs to synthetic and proliferating phenotype, resulting in medial layer degeneration and aortic aneurysm formation 204, 206.…”

Next generation MicroRNA sequencing to identify coronary artery disease patients at risk of recurrent myocardial infarction

“…Most studies using miRNA as biomarkers have focused on circulating miRNA from plasma [15], while fewer studies have employed miRNA derived from fixed whole blood, which includes miRNA derived from platelets and leukocytes [16–18]. In concept, novel miRNA biomarkers may potentially be used to monitor effects of medical therapy on gene expression and posttranslational modifications.…”