Genome-wide expression profiling of the perivascular adipose tissue in abdominal aortic aneurysm

Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of diseases of large vessels, including abdominal aortic aneurysm (AAA). We tested the hypothesis that locally restricted transcriptional profiles characterize PVAT surrounding AAA. Using a genome-wide approach, we investigated the PVAT transcriptome of AAA in 30 patients with either large (≥55 mm) or small (<55 mm) aneurysm diameter. We performed a data adjustment step using the DaMiRseq R/Bioconductor package, to remove the effect of confounders as produced by high-throughput gene expression techniques. We compared PVAT of AAA with PVAT of not-dilated abdominal aorta of each patient to limit the effect of inter-individual variability, using the limma R/Bioconductor package. We found highly consistent differences in PVAT gene expression clearly distinguishing PVAT of AAA from PVAT of not-dilated aorta, which increased in number and magnitude with increasing AAA diameter. These changes did not systemically affect other abdominal adipose depots (omental or subcutaneous fat). We dissected putative mechanisms associated with PVAT involvement in AAA through a functional enrichment network analysis: both innate and adaptive immune-response genes along with genes related to cell-death pathways, metabolic processes of collagen, sphingolipids, aminoglycans and extracellular matrix degradation were strongly overrepresented in PVAT of AAA compared with PVAT of not-dilated aorta. Our results provide support to a possible role of PVAT in AAA pathogenesis and suggest that AAA is an immunologic disease with an underlying autoimmune component. These disease-specific expression signatures could help identifying pharmacological targets for preventing AAA progression. A paired-sample study design was used to reduce the problem of inter-individual variations. Thirty male patients with either large (≥55 mm, n=7) or small (<55 mm, n=23) aneurysm diameter were consecutively enrolled. Diverse adipose tissue (AT) depots were safely obtained sequentially, in the following order: subcutaneous abdominal fat, omental-visceral fat, periaortic fat obtained from the aortic neck proximal to the aneurismal sac (non-dilated perivascular adipose tissue, ND-PVAT), and periaortic fat surrounding the aneurysmal sac (dilated perivascular adipose tissue, D-PVAT). RNA was extracted from 50-100 mg of frozen AT samples. RNA samples of poor quality and yield were discarded.