Next Step Towards Precision Medicine in Thoracic Aortic Disease—The Potential of Long Noncoding RNAs

Background: The emergence of precision medicine in diagnostics and therapy of aortic diseases drives the understanding of molecular pathways. Noncoding RNAs, in particular long noncoding RNA (lncRNA), offers new opportunities in understanding aortic pathologies. Here, we describe two promising representatives and their pathological implications in thoracic aortic diseases by comparing areas with and without wall shear stress and consecutive dilation.

Methods: The lncRNAs TMEM72-AS1 and LINC00632 were identified by preliminary single-cell RNA sequencing on thoracic ascending aortic aneurysm (TAA). Both are almost uniquely expressed in vascular smooth muscle cells and differed between the outer (dilated) and inner curvature. Expression was further analyzed by qPCR in 90 samples of TAA, comparing inner and outer curvature. In addition, analyses were performed according to aortic valve morphology (bicuspid - BAV, tricuspid - TAV) and pathology (stenosis - AS, regurgitation - AI). As control, expression was validated in seven healthy aortic samples from heart transplant donors. qPCR CT values greater than 40 were excluded. The results were indicated as multiple of the expression at the inner curvature, which was set to 1.

Results: Quantitative expression analysis showed significantly higher expression of TMEM72-AS1 and LINC00632 in dilated areas (2.1, p < 0.001; 1.83, p < 0.05, respectively). LINC00632 exhibited highly significant expression, particularly in tissues from BAV and AI (2.28, p < 0.001; 1.99, p < 0.01; 2.16, p < 0.01, respectively). Conversely, TMEM72-AS1 had no significant difference in tissues from AI samples. No differences in expression were detected for both lncRNAs in healthy aortic tissue.

TMEM72-AS1		LINC00632
	Expression (mean ± SD)		Expression (mean ± SD)
TAA; n = 87	1.83 ± 3.22; p < 0.05	TAA; n = 76	2.28 ± 2.08; p < 0.001
BAV(54.0%)	1.49 ± 1.72; p < 0.05	BAV (52.6%)	1.99 ± 1.69; p < 0.01
TAV (41.4%)	1.68 ± 1.77; p < 0.05	TAV (46.1%)	2.19 ± 2.48; p < 0.05
AI (57.5%)	1.32 ± 1.12; ns	AI (56.6%)	2.16 ± 2.15; p < 0.01
AS (41.4%)	2.60 ± 4.73; p < 0.05	AS (43.4%)	2.02 ± 1.99; p < 0.05

Conclusion: The expression of lncRNAs TMEM72-AS1 and LIN00632 was significantly increased in dilated areas with potentially more wall shear stress and thus, represents an interesting target for potential diagnostic and therapeutic measures.

 

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

Publication History

Article published online:
13 February 2024