Genome-Wide Expression Profiling Unveils Autoimmune Response Signatures in the Perivascular Adipose Tissue of Abdominal Aortic Aneurysm

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Abstract

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 ECM (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.

Original languageEnglish
Pages (from-to)ATVBAHA118311803
JournalArteriosclerosis, Thrombosis, and Vascular Biology
DOIs
Publication statusE-pub ahead of print - Dec 20 2018

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Abdominal Aortic Aneurysm
Autoimmunity
Adipose Tissue
Genome
Gene Expression
Aorta
Sphingolipids
Data Mining
Subcutaneous Fat
Abdominal Aorta
Immune System Diseases
Adaptive Immunity
Transcriptome
Innate Immunity
Genes
Extracellular Matrix
Blood Vessels
Homeostasis
Cell Death
Collagen

Cite this

@article{e00a59a9da564bdd8e62f30414f1ed24,
title = "Genome-Wide Expression Profiling Unveils Autoimmune Response Signatures in the Perivascular Adipose Tissue of Abdominal Aortic Aneurysm",
abstract = "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 ECM (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.",
author = "Luca Piacentini and {Pablo Werba}, Jos{\'e} and Elisa Bono and Claudio Saccu and Elena Tremoli and Rita Spirito and {Ivanoe Colombo}, Gualtiero",
year = "2018",
month = "12",
day = "20",
doi = "10.1161/ATVBAHA.118.311803",
language = "English",
pages = "ATVBAHA118311803",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Genome-Wide Expression Profiling Unveils Autoimmune Response Signatures in the Perivascular Adipose Tissue of Abdominal Aortic Aneurysm

AU - Piacentini, Luca

AU - Pablo Werba, José

AU - Bono, Elisa

AU - Saccu, Claudio

AU - Tremoli, Elena

AU - Spirito, Rita

AU - Ivanoe Colombo, Gualtiero

PY - 2018/12/20

Y1 - 2018/12/20

N2 - 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 ECM (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.

AB - 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 ECM (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.

U2 - 10.1161/ATVBAHA.118.311803

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JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

ER -