Abstract 39: Circulating MiRNA Signature of Pet-Positive Abdominal Aortic Aneurysms: New Potential Predictors of Rupture
Prediction of abdominal aortic aneurysm (AAA) rupture by specific biomarkers is a challenging issue in the field of vascular diseases. Small non-coding RNAs, miRNAs, are potent post-transcriptional regulators of gene expression and were found to be present in blood and to represent valuable biomarkers for a variety of diseases, notably in cancer. Recently, we showed that a positive uptake of 18F-fluorodeoxyglucose (FDG) in the aneurysmal wall observed by positron emission tomography (PET) was correlated with a higher instability of the wall which could lead to its rupture. Identifying circulating miRNAs correlated with a positive PET could help discriminating patients at higher risk of rupture.
The expression level of 372 miRNAs was evaluated by using the miScript PCR system (Qiagen) in the plasma of 45 AAA patients among whom 24 had no FDG uptake (A0) and 21 displayed a positive PET (A+). In a first approach, 4 pools of plasma samples from the A0 and the A+ groups were analyzed. 14 miRNAs were found significantly modulated (8 downregulated and 6 upregulated, p<0.05) in A+ as compared to A0 patients. The modulation of expression of 8 of these miRNAs was validated by qRT-PCR on the individual samples. Among the decreased miRNA, miR-204-5p has been previously found to be downregulated in the aneurysmal wall compared to healthy aortas. These 8 miRNAs found modulated in blood were then analyzed in the media of A+ wall at the FDG uptake site and compared to a negative site of the aneurysm from the same patient. Two of these 8 miRNAs, miR-125b-5p and miR-204-5p, were significantly downregulated in the FDG uptake site in 6 patients.
In conclusion, 8 circulating miRNAs might represent a new signature of PET+ AAA, at high risk of rupture. Moreover, 2 of them are significantly downregulated in the metabolically active aneurysmal wall prone to rupture. It is noteworthy that a validated target of miR-125b-5p is MMP13, a collagenase that we previously showed to be largely increased in the positive FDG uptake site of adventitia and that could be potentially involved in the ultimate degradation of collagen leading to aneurysmal rupture.
Author Disclosures: A. Courtois: None. B. Nusgens: None. R. Hustinx: None. J. Defraigne: None. A. Colige: None. N. Sakalihasan: None.
- © 2015 by American Heart Association, Inc.