Abstract
Perivascular adipose tissue (PVAT) helps regulate arterial homeostasis and plays a role in the pathogenesis of large vessel diseases. In this study, we investigated whether the PVAT of aortic occlusive lesions shows specific gene-expression patterns related to pathophysiology. By a genome-wide approach, we investigated the PVAT transcriptome in patients with aortoiliac occlusive disease. We compared the adipose layer surrounding the distal aorta (atherosclerotic lesion) with the proximal aorta (plaque-free segment), both within and between patients with complete aortoiliac occlusion (Oc) and low-grade aortic stenosis (St). We found that PVAT of the distal versus proximal aorta within both Oc- and St-patients lacks specific, locally restricted gene-expression patterns. Conversely, singular gene-expression profiles distinguished the PVAT between Oc- and St-patients. Functional enrichment analysis revealed that these signatures were associated with pathways related to metabolism of cholesterol, vessel tone regulation, and remodeling, including TGF-β and SMAD signaling. We finally observed that gene-expression profiles in omental-visceral or subcutaneous fat differentiated between Oc- and St-patients, suggesting that the overall adipose component associates with a different atherosclerosis burden. Our work points out the role of PVAT and, likely, other adipose tissues play in the pathophysiological mechanisms underlying atherosclerotic disease, including the abdominal aortic occlusive forms.
Highlights
Perivascular adipose tissue (PVAT) helps regulate arterial homeostasis and plays a role in the pathogenesis of large vessel diseases
We have shown that disease-specific gene expression patterns are locally-restricted to the PVAT surrounding abdominal aortic aneurysms (AAA) in human patients, that these molecular signatures are suggestive of an autoimmune response, and that changes in gene expression have increased in number and magnitude with disease extent and progression[17]
PVAT is a well-recognized regulator of vessel homeostasis and its dysfunction may strongly influence the pathogenesis of vascular diseases[21,22]
Summary
Perivascular adipose tissue (PVAT) helps regulate arterial homeostasis and plays a role in the pathogenesis of large vessel diseases. We investigated whether the PVAT of aortic occlusive lesions shows specific gene-expression patterns related to pathophysiology. Our work points out the role of PVAT and, likely, other adipose tissues play in the pathophysiological mechanisms underlying atherosclerotic disease, including the abdominal aortic occlusive forms. Even so, increasing evidences suggest that dysfunctional perivascular adipose tissue (PVAT) participates in the development and progression of both atherosclerotic and nonatherosclerotic vascular diseases[8,9], including those affecting the distal abdominal aorta. We have shown that disease-specific gene expression patterns are locally-restricted to the PVAT surrounding abdominal aortic aneurysms (AAA) in human patients, that these molecular signatures are suggestive of an autoimmune response, and that changes in gene expression have increased in number and magnitude with disease extent and progression[17]
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