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Transcriptome analysis of the perivascular adipose tissue in peripheral artery disease patients

ABSTRACT: Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of diseases of large vessels. We tested the hypothesis that locally restricted transcriptional profiles characterize the PVAT localized at the site of the obstruction of the abdominal aorta in peripheral artery disease (PAD) patients. By a genome-wide approach and a paired-samples design, we investigated the PVAT transcriptome of 11 PAD patients with occlusive and with stenotic abdominal aortic lesions. 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 the distal versus the proximal aorta of each patient to limit the effect of inter-individual variability, using the limma R/Bioconductor package. We did not find consistent differences in PVAT gene expression clearly distinguishing the two PVAT of the same patient. However, we found significant differences by comparing patients with total occlusive versus those with stenotic abdominal aortic lesions. We dissected putative mechanisms associated with PVAT involvement in PAD patients with total occlusive and with stenotic abdominal aorta lesions through a functional enrichment network analysis: cholesterol, sterol and alcohol biosynthetic process were enriched in patients with total occlusive lesions, whereas pathways recalling the structure maintenance and remodeling of the vessels were associated with patients with stenotic lesions. Our results would suggest that the PVAT transcriptome at the distal aorta site is associated with the degree of the atherosclerotic burden in PAD patients and that this effect can probably account for a diffuse (systemic) process affecting homogenously the PVATs spanning along the distal aorta rather than a singular specific trait.

ORGANISM(S): Homo sapiens

PROVIDER: GSE136822 | GEO | 2020/04/20

REPOSITORIES: GEO

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Project description:Thoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared to white adipose tissue (WAT), PVAT and BAT from C57BL/6 mice fed a high fat diet for 13 weeks had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80, CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b+/CD11c+ macrophages in BAT (1.0%) in comparison to WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from thermal and inflammatory stress. 8-week-old male C57BL6/J mice were fed a normal (ND) or high fat diet (HFD) (Research Diets 12451, 45 kcal% fat) for 13 weeks. Mice were then euthanized and four different adipose depots were harvested for RNA analysis: perivascular fat from the lesser curvature of the aortic arch (PVAT), interscapular brown adipose (BAT), inguinal adipose tissue (SAT), and epididymal adipose tissue (VAT). 250 ng total RNA pooled from two mice was used for cDNA synthesis; 3 biological replicates per tissue and diet were performed for a total of 24 hybridizations.

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Transcriptome analysis of the perivascular adipose tissue in peripheral artery disease patients

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