Long Noncoding RNAs CARMN, LUCAT1, SMILR, and MALAT1 in Thoracic Aortic Aneurysm: Validation of Biomarkers in Clinical Samples

الملخص EN

Background and Objectives.

Thoracic aortic aneurysm (TAA) is a silent disease characterised by aortic wall expansion and vascular smooth muscle cell (VSMC) dedifferentiation from contractile to synthetic phenotype.

Long noncoding RNAs (lncRNAs) involved in VSMC phenotypic regulation could be considered as potential diagnostic indicators and therapeutic targets of TAA.

In vitro studies show that lncRNAs CARMN, LUCAT1, MALAT1, and SMILR are associated with the VSMC phenotypic state.

Our aim was to test if these lncRNAs are dysregulated during TAA formation in clinical patient samples.

Materials and Methods.

Relative expression of lncRNAs CARMN, LUCAT1, SMILR, and MALAT1 was tested in clinical aortic tissue and blood plasma samples from TAA and non-TAA patients using the qRT-PCR method.

The Mann–Whitney U test was used to compare ΔCt values between the study groups.

ROC curve analysis was performed to evaluate the diagnostic value of plasma lncRNAs.

Results.

We found significantly reduced CARMN (p=0.033) and LUCAT1 (p=0.009) expression in aortic tissue samples from TAA patients.

Relative expression of MALAT1 (p=0.117) and SMILR (p=0.610) did not differ in aortic tissue between the TAA and non-TAA groups.

Expression of both LUCAT1 and SMILR was significantly decreased in TAA patients’ blood plasma compared to controls (p=0.018 and p=0.032, respectively).

However, only LUCAT1 showed the ability to discriminate aneurysmal disease in patients’ blood plasma (AUC=0.654, 95%CI=0.534‐0.775, p=0.018).

Conclusions.

We have shown that the expression of lncRNAs CARMN and LUCAT1 is reduced in dilated aortic tissue and that the LUCAT1 and SMILR expression is lower in the blood plasma of TAA patients.

Decreased LUCAT1 expression in TAA patients’ blood plasma may have diagnostic potential in discriminating patients with TAA.