A microRNA profile comparison between thoracic aortic dissection and normal thoracic aorta indicates the potential role of microRNAs in contributing to thoracic aortic dissection pathogenesis

ObjectivesOur aim was to identify important microRNAs (miRNAs) that might play an important role in contributing to aortic dissection by conducting a miRNA profile comparison between thoracic aortic dissection (TAD) and normal thoracic aorta.MethodsThe differentially expressed miRNA profiles of the aortic tissue between TAD patients (n = 6) and age-matched donors without aortic diseases (NA; n = 6) were analyzed by miRNA microarray. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was further performed to verify the expression of 12 selected miRNAs with an increased number of samples (TAD n = 12; NA n = 8). The potential targets of the differentially expressed miRNAs were predicted using computational searches. Bioinformatic analyses of the predicted target genes (gene ontology, pathway and network analysis) were done for further research. Additionally, Western blotting was performed to confirm the bioinformatics findings.ResultsThe miRNA microarray revealed differentially expressed miRNAs between the TAD and NA groups. In the TAD group, 18 miRNAs were upregulated and 56 were downregulated (fold change >2, P < .01). qRT-PCR verified statistically consistent expression of seven selected miRNAs with microarray analysis. Combined with our previous proteomics study, target gene prediction revealed that some miRNAs reciprocally expressed with their targeted proteins. Target gene-related pathway analysis showed a significant change in five pathways in the TAD group compared with the NA group, especially the focal adhesion and the mitogen-activated protein kinase (MAPK) signaling pathways. By further conducting miRNA gene network analysis, we found that the mir-29 and mir-30 families are likely to play a role in the regulation of these two pathways, respectively.ConclusionsOur results indicate that miRNAs expression profiles in aortic media from TAD were significantly changed. These results may provide important insights into TAD disease mechanisms. This study also suggests that the focal adhesion and MAPK signaling pathways might play important roles in the pathogenesis of TAD.Clinical RelevanceTAD is a life-threatening disease with high mortality rates whose underlying mechanism remains unclear. The miRNAs usually negatively modulate gene expression at the post-transcriptional level. Studying both the disease-related proteins and miRNAs in conjunction with the intermodulation between them can offer clarifications to the molecular mechanism of the disease and provide more reliable molecular targets for prevention and treatment. Each possible miRNA gene pair we identified in this study is a strong candidate for a major study aimed at definitively confirming the presence of specific miRNA gene interactions, and providing possible molecular targets for prevention and treatment of the disease