173 - Transcriptome profiling of the perivascular adipose tissue of aortic occlusive disease reveals dysregulation of genes involved in vessel tone and remodelling (ID 1006)
Abstract
Background and Aims
Perivascular adipose tissue (PVAT) helps regulate arterial homeostasis and can play a role in the pathogenesis of large vessel diseases. We investigated whether the PVAT of aortic occlusive lesions displays specific, pathophysiology-linked gene-expression patterns.
Methods
We enrolled eleven patients (51-79 years) with peripheral artery disease undergoing elective surgery, presenting with either an aortoiliac occlusive disease (AIOD, n=6) or diffuse stenosis of the common iliac arteries and/or aorta (n=5). Using a microarray-based genome-wide approach, we compared the transcriptome of the PVAT surrounding the distal aorta (atherosclerotic lesion) vs. the proximal aorta (plaque-free segment) and vs. other adipose tissue (AT) depots, both within and between groups. Cutting-edge data mining procedures allowed increasing the overall sensitivity and power of the analysis.
Results
We found that the PVAT of the distal aorta in both AIOD and stenotic patients lacks locally restricted gene-expression patterns. On the contrary, a specific gene expression profile distinguished the PVAT of AIOD from stenotic patients, irrespective of fat localization (perilesional or proximal). Functional enrichment analysis revealed that this signature was associated with pathways related to cholesterol metabolism, vessel tone regulation, and remodelling, including TGF-β and SMAD signalling. We observed that also gene-expression profiles in omental-visceral or subcutaneous fat were able to distinguish between the two patient groups, suggesting that the atherosclerosis burden is associated with systemic alterations in AT.
Conclusions
Our work sheds new light on the potential role of PVAT and, possibly, other adipose tissues in the pathophysiological mechanisms underlying peripheral atherosclerotic disease, including the abdominal aortic occlusive forms.
