Abstract 237: MicroRNA patterns in Abdominal Aortic Aneurysm Appear to Reflect Adventitial Inflammation

Abstract

MicroRNAs (miRNA) have been shown to play an important role in vascular biology. In this study we examined the miRNA profile within human abdominal aortic tissue and plasma to identify differential expression patterns between aneurysm cases and controls.

Whole miRNome profiles were assessed using array-based assays (Affymetrix miRNA 2.0) in 27 AAA and 14 control aortic biopsies. Results were validated in 89 AAA and 21 controls using real-time PCR (Taqman-based) assays. A subset of case and control aortic samples were also microdissected. Separate intima/medial and adventitial miRNome profiles were compared with matching total wall. In addition, whole miRNome profiles of EDTA plasma from 22 AAA and 20 age and gender matched controls were examined and validated by RT-PCR in 62 AAA and 62 control plasmas.

In aortic tissue, 18 miRNA were highly significantly (p<1x10-4, q<1x10-3) differentially expressed in AAA versus controls. Variable principal component analysis indicated that these miRNA were expressed in three distinct clusters. MiRNA within each cluster were subsequently validated by RT-PCR. The strongest validated associations were miR-146a (p<0.0004), mir-150 (p<0.001), miR-223 (p<0.0001), and mir-140-3p (p=0.006). Aortic wall sub-layer analysis indicated that total wall miRNA profiles reflected adventitial related miRNA in AAA and intima/medial related miRNA in controls.

In plasma, 12 miRNA were initially identified (including three which were also observed in tissue) however only miR-151-5p (p=0.005) was successfully validated by RT-PCR.

The general pattern of AAA associated miRNA expression indicated regulation of genes known to be involved with B-cell and T-cell function. This was also consistent with the concentration of these miRNA within the AAA adventitia, as these cells are key regulators of the vascular (adventitial) inflammation associated with AAA.

In conclusion, microRNAs appear to have significant potential as AAA biomarkers. However, further work is required to determine the specificity of such associations to account for potential confounders, including as concurrent arterial disease.