Long Non-coding RNAs: Emerging Biomarkers in Thoracic Aortic Aneurysms

Background: The complex pathophysiology of thoracic aortic aneurysm (TAA) remains only partially understood. Recent research highlights the role of long non-coding RNAs (lncRNAs) as key regulators of gene expression, potentially influencing aneurysm development. This study aims to explore the differential expression of specific lncRNAs in various regions of the aortic wall in TAA patients with different aortic valve pathologies and morphologies.

Methods: Promising lncRNAs were identified by performing single cell RNA sequencing (scRNAseq) in TAA aortas (n = 7). For further expression analysis RT-qPCR comparing the outer curvature (OC, dilated) with the inner curvature (IC, not dilated) was done in a higher sample number (n = 80) categorized into groups of 20: TAA with aortic insufficiency (AI) or stenosis (AS), with tricuspid (TAV) or bicuspid aortic valves (BAV). Healthy tissue was obtained from transplant (HTX) aortas (n = 10). Results were expressed as multiples of IC expression (set to 1). Tissue was provided by the cardiac surgery biobank at LMU Hospital.

Results: ScRNAseq analysis revealed 4 different VSMC clusters and identified the lncRNAs NEAT1, ADAMTS9-AS2, NORAD, LINC00910, LINC01578, and MIR100HG as promising representatives. Expression analysis showed significant increases in NEAT1 (1.36 ± 0.02, p = 0.01), ADAMTS9-AS2 (1.73 ± 0.02, p = 0.004), NORAD (1.19 ± 0.01, p = 0.03), LINC00910 (1.47 ± 0.02, p = 0.002), LINC01578 (1.22 ± 0.02, p = 0.006), and MIR100HG (1.60 ± 0.01, p < 0.0001) in the OC compared with the IC, with further abnormalities noted within the subgroups. Notably, NEAT1 expression was significantly elevated in BAV TAAs (1.42 ± 0.03, p = 0.03), LINC00910 in AI TAAs (1.61 ± 0.03, p = 0.01), and LINC01578 in TAV TAAs (1.44 ± 0.05, p = 0.01). Interestingly, the most pronounced differences were seen in ADAMTS9-AS2 (1.54 ± 0.04, 2.15 ± 0.06, 1.92 ± 0.05, and 1.56 ± 0.04, p < 0.05) and MIR100HG (1.47 ± 0.02, 1.74 ± 0.03, 1.6 ± 0.02, and 1.63 ± 0.02, p < 0.001), which were significantly more prominent in the OC across BAV, TAV, AI, and AS, respectively.

Conclusion: This study provides novel insights into the differential expression of lncRNAs in the ascending aortic wall, highlighting their potential as non-invasive prognostic and diagnostic biomarkers. The stable nature of lncRNAs in bodily fluids and their disease-specific expression patterns make them promising candidates for clinical applications. However, further research is required to overcome the challenges in translating these findings into clinical practice.

NB: This abstract was presented in a similar form at a previous meeting.

Publication History

Article published online:
11 February 2025