Abstract
Acute aortic dissection (AAD) is a life-threatening cardiovascular disease with the high morbidity and mortality. Imaging modalities are the gold standard for the diagnosis of AAD; however, they are not always available in emergency department. Biomarker-assisted diagnosis is important for the early treatment of AAD. The aim of the present study was to identify potential microRNA (miRNA) biomarkers for AAD. Differentially expressed plasma miRNAs between AAD patients and age-matched healthy volunteers were analyzed by miRNA microarray. Quantitative RT-PCR was further performed to verify the expression of selected miRNAs (miR-4787-5p and miR-4306) with an increased number of samples. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of miR-4787-5p and miR-4306 as biomarkers for distinguishing AAD. Using TargetScan and miRanda, miR-4787-5p and miR-4306 were selected to predict target gene related to cytokines detecting by dual luciferase assay and western blotting. Nine upregulated and twelve downregulated miRNAs were identified in the circulating plasma of AAD patients. qRT-PCR verified statistically consistent expression of two selected miRNAs with microarray analysis. ROC analyses demonstrated that miR-4787-5p and miR-4306 were specific and sensitive for the early diagnosis of AAD. Bioinformatic predictions and dual luciferase assay suggested that polycystin-1 (PKD1) and transforming growth factor-β1 (TGF-β1) were respectively direct target of miR-4787-5p and miR-4306. Furthermore, the protein expression of the downstream targets of PKD1 and TGF-β1 were significantly reduced following overexpression of miR-4787-5p and miR-4306. These results revealed that miR-4787-5p and miR-4306 could be developed as diagnostic potential biomarkers for AAD, and they could be involved in the pathogenesis of AAD.