In 30 patients with AAA, perivascular adipose tissue of the dilated aorta showed substantial gene expression differences versus non-dilated aorta, overrepresenting immune and cell-death pathways.
Observational (n=30)
Genome-wide expression profiling reveals that perivascular adipose tissue surrounding abdominal aortic aneurysms exhibits distinct autoimmune, inflammatory, and matrix degradation transcriptional signatures compared to non-dilated aorta.
Objective- Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of large vessel diseases, including abdominal aortic aneurysm (AAA). Herein, we tested the hypothesis that locally restricted transcriptional profiles characterize PVAT surrounding AAA, indicating specific dysfunctions associated with the disease. Approach and Results- Using a paired sample design to limit the effects of interindividual variation, we performed a microarray-based investigation of the PVAT transcriptome in 30 patients with AAA, comparing the adipose layer of the dilated abdominal aorta with that of the not-dilated aortic neck in each patient. Furthermore, we used a state-of-the-art data mining procedure to remove the effect of confounders produced by high-throughput gene expression techniques. We found substantial differences in PVAT gene expression clearly distinguishing the dilated from the not-dilated aorta, which increased in number and magnitude with increasing AAA diameter. Comparisons with other adipose depots (omental or subcutaneous fat) confirmed that gene expression changes are locally restricted. We dissected putative mechanisms associated with AAA PVAT dysfunction 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 the not-dilated aorta. Conclusions- Our results support a possible function of PVAT in AAA pathogenesis and suggest that AAA is an immunologic disease with an underlying autoimmune component. Interfering with these disease-specific pathways would clarify their precise role in AAA pathogenesis.
Piacentini et al. (Thu,) conducted a observational in Abdominal aortic aneurysm (n=30). Perivascular adipose tissue of dilated abdominal aorta vs. Perivascular adipose tissue of not-dilated aortic neck was evaluated on PVAT transcriptome differences. In 30 patients with AAA, perivascular adipose tissue of the dilated aorta showed substantial gene expression differences versus non-dilated aorta, overrepresenting immune and cell-death pathways.