The Potential of Long Non-Coding RNAs in Thoracic Aortic Disease: Pathophysiological Examinations and Possible Clinical Implications

Objective: The comprehension of molecular signaling pathways is driven by the trend towards patient-specific therapies. Non-coding RNAs, specifically long non-coding RNAs (lncRNAs), provide novel opportunities to comprehend aortic pathologies. In this article, we describe two promising representatives and their pathological implications in thoracic aortic disease by comparing regions with and without wall shear stress and subsequent dilatation.

Methods: Preliminary single-cell RNA sequencing on thoracic ascending aortic aneurysm (TAA) identified the lncRNAs TMEM72-AS1 and LINC00632. Both are almost exclusively expressed in vascular smooth muscle cells and exhibit differences between the outer (dilated) and inner curvature. Expression was analyzed by qPCR in 110 samples of TAA and acute aortic dissection (AADA), comparing the inner and outer curvature. Analyses were also performed based on aortic valve morphology (bicuspid - BAV, tricuspid - TAV) and pathology (stenosis - AS, regurgitation - AI). As a control, expression was validated in seven healthy aortic samples from heart transplant donors. CT values greater than 40 were excluded. The results were expressed as multiples of the expression at the inner curvature, which was set to 1.

Results: Quantitative expression analysis revealed significantly higher expression of TMEM72-AS1 and LINC00632 in dilated areas (1.93, p<0.001; 1.96, p<0.001). LINC00632 exhibited highly significant expression in TAA samples, particularly in tissues from bicuspid aortic valve (BAV) and aortic regurgitation (AR) (2.1, p<0.001; 1.99, p<0.01; 2.16, p<0.01). However, there was no significant difference in samples from acute aortic dissection (AADA) tissues. In contrast, TMEM72-AS1 exhibited higher expression in tissues from AADA (1.67, p<0.05), but showed no significant difference in tissues from BAV samples. Both lncRNAs showed no differences in expression in healthy aortic tissue.

Conclusion: The expression of lncRNAs TMEM72-AS1 and LIN00632 was significantly increased in dilated areas with higher wall shear stress. Therefore, they represent potential targets for diagnostic and therapeutic measures.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
11 June 2024