Dysregulated long non-coding RNAs involved in regulation of matrix degradation during type-B aortic dissection pathogenesis.

Abstract

Thoracic aortic dissection (TAD) is a catastrophic disease with the rupture of aortic media resulted mainly from the degradation of extracellular matrix. With the deep study of long non-coding RNAs (lncRNAs) in cardiovascular diseases, the correlation between lncRNAs and the TAD pathogenesis is under revealed. In this study, we aimed to screen the differentially expressed lncRNAs involved in the regulation of matrix degradation during type-B aortic dissection (TBAD), whose pathogenesis is more similar to atherosclerosis. A total of 393 aberrantly expressed lncRNAs and 432 aberrantly expressed mRNAs were identified in the descending aortic samples from TBAD patients. Then, co-expression analysis was applied to analyze the correlation between the top five differentially expressed lncRNAs and aberrantly expressed mRNAs, so as to screen the lncRNAs involved in the regulation of matrix degradation. The results showed that two transcripts from lnc-TNFSF14 (lnc-TNFSF14-2, and lnc-TNFSF14-3) were negatively interacted with MMP14 and MMP19. Subsequently, quantitative real-time PCR assay confirmed that lnc-TNFSF14-2 were negatively correlated with MMP14 (rs = - 0.8180) and MMP19 (rs = - 0.8449), and lnc-TNFSF14-3 was also negatively correlated with MMP14 (rs = - 0.7098) and MMP19 (rs = - 0.7728) in descending aorta from TBAD patients (n = 20). Overall, our study found the aberrant lncRNAs expression profiles in TBAD, and identified lnc-TNFSF14 as a potential target regulating matrix degradation. The results also provided crucial clues for lncRNAs function research on TBAD development.