Genome-wide expression profiling of the perivascular adipose tissue in abdominal aortic aneurysm
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PROVIDER: PRJNA490103 | ENA |
REPOSITORIES: ENA
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Project description:Background: Perivascular adipose tissue (PVAT) is a key regulator of vascular dysfunction. Impairment of PVAT phenotypic plasticity with aging may play a role in vascular pathology including abdominal aortic aneurysms (AAA). Yet, the mechanisms underlying PVAT plasticity in aneurysm pathogenesis remain elusive. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on perivascular stromal cells (PVSCs) from young (2-3-month-old) and aged (18-20-month-old) mice. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) was measured in PVAT of aged mice and human aneurysm samples. Loss- and gain-of-function approaches were employed to investigate the role of SM22α-lineage PVSCs-derived PGC-1α in aneurysm development. Molecular mechanisms were explored through transcriptome and functional studies in young and aged mice, SM22αCre; Rosa26RFP/+; PGC1αf/f and SM22αCre; Rosa26RFP/+ mice with angiotensin II (AngII)- and DOCA/salt- induced AAA models. Results: SM22α+ cells accumulated in PVAT of angiotensin II-treated aged mice and patients with aortic aneurysms. scRNA-seq analysis revealed that aging disrupted the differentiation potential of SM22α-lineage PVSCs and led to reduced PGC-1α level. PGC1α downregulation in PVAT was observed in both mice AAA models and human aneurysm lesions. In mice with SM22α-driven PGC-1α-deletion AngII induced AAA formation was accompanied by PVSC-to-myofibroblast differentiation. in vitro PGC1α-knockdown suppressed nuclear YAP signaling, reducing adipocyte differentiation, while increasing MMP2-secreting myofibroblasts. Furthermore, PGC-1α overexpression in aged mice or administration of the YAP signaling inhibitor Verteporfin in SM22αCre; Rosa26RFP/+; PGC1αf/f mice restored PVAT function and conferred protection against aneurysm formation. Lastly, we employed the radiomics analysis to non-invasively evaluate PVAT in the context of AAA severity in humans. Conclusions: PGC-1α deficiency in SM22α-lineage stromal cells disrupts the balance between adipogenic and myofibrogenic differentiation through regulating the YAP signaling, ultimately promoting aneurysm development. Radiomics assessment may present a promising noninvasive approach for PVAT evaluation in aneurysms, offering valuable potential for clinical research.
2025-05-09 | GSE293558 | GEO
Project description:Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of diseases of large vessels, including abdominal aortic aneurysm (AAA). We tested the hypothesis that locally restricted transcriptional profiles characterize PVAT surrounding AAA. Using a genome-wide approach, we investigated the PVAT transcriptome of AAA in 30 patients with either large (≥55 mm) or small (<55 mm) aneurysm diameter. 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 AAA with PVAT of not-dilated abdominal aorta of each patient to limit the effect of inter-individual variability, using the limma R/Bioconductor package. We found highly consistent differences in PVAT gene expression clearly distinguishing PVAT of AAA from PVAT of not-dilated aorta, which increased in number and magnitude with increasing AAA diameter. These changes did not systemically affect other abdominal adipose depots (omental or subcutaneous fat). We dissected putative mechanisms associated with PVAT involvement in AAA 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 not-dilated aorta. Our results provide support to a possible role of PVAT in AAA pathogenesis and suggest that AAA is an immunologic disease with an underlying autoimmune component. These disease-specific expression signatures could help identifying pharmacological targets for preventing AAA progression.
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Project description:SM22α-lineage stromal cells in perivascular adipose tissue contribute to abdominal aortic aneurysm
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Project description:Abdominal aortic aneurysm (AAA) is a vascular disease with high incidence at present.There is no effective drug treatment. MicroRNAs(miRNAs) play a regulatory role in the occurrence and development of AAA,and miRNA therapy is a promising treatment for AAA. The purpose of this study was to explore the differential expression of miRNAs in abdominal aorta of ApoE-/- AngII-induced abdominal aortic aneurysm mices. We used miRNA array to analyze miRNA differences in abdominal aorta between mices with ApoE-/- AngII-induced abdominal aortic aneurysm and ApoE-/-.
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Project description:Angiotensin II (Ang II)-induced abdominal aortic aneurysm model was established in low-density lipoprotein receptor-deficient mice, and the gene expression profiles in abdominal aortic tissues exhibiting varying degrees of severity were analyzed.
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Project description:Abdominal aortic aneurysm (AAA) is a permanent segmental dilatation of the abdominal aorta, contributing to a high mortality once rupture. We performed RNA-sequencing analysis of abdominal aorta tissues from 14 participants, including seven patients with AAA and seven control individuals.
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Project description:We have employed circRNA microarray expression profiling as a discovery platform to identify the dysregulated circRNAs in human abdominal aortic aneurysm.
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