A molecular fingerprint for terminal abdominal aortic aneurysm progression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE98278 | GEO | 2018/02/27
REPOSITORIES: GEO
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Project description:An abdominal aortic aneurysm (AAA) is a pathological dilatation of the aortic wall and it is a life-threatening disease due to the risk of rupture. Currently, surgical intervention remains the only definitive treatment recommended for large or rapidly expanding aneurysms. No pharmacological therapy is currently available to prevent AAA progression, as no drug has been proven effective. Diabetes is a major risk factor for cardiovascular disease in general. However, many studies over the last decade show that type 2 diabetes patients have a lower incidence of AAA and a slower aneurysm growth rate, which has been correlated with metformin use. We performed a proteomics analysis on resected aortic tissue from controls, non-diabetic (ND) and diabetic (D) AAA patients.
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Project description:This study investigates intra- and inter-individual RNA genome-wide expression profiling differences (Illumina HumanHT-12, BeadCHIP expression) of AAA (abdominal aortic aneurysms) biopsies from 12 patients. Biopsies were collected during open surgical AAA repair and according to prior finite element analysis (FEA) from regions with highest and lowest wall stress.
2022-06-02 | GSE205071 | GEO
Project description:There is no effective pharmacotherapy to prevent the growth and rupture of abdominal aortic aneurysms (AAA), a leading cause of death. We developed a novel preclinical model showing that the interaction of bona fide risk factors (i.e., cigarette smoke (CS) and hypercholesterolemia) induced AAA formation, rupture, and death. Elastin fragmentation resulted from CS-induced exacerbation of the atherosclerotic process, significant given atherosclerosis is a disease of the inner intimal layer of the artery, with the media remaining largely intact. Importantly, arterial injury was driven by CSF-1-dependent macrophages (Mφ) accumulating within developing atherosclerotic plaques that exhibited tissue degrading proteolytic activity in vivo. Single-cell RNA sequencing further demonstrated conservation of Mφ responses in atherosclerotic plaque from murine and human AAA. Our findings advance understanding of the pathological sequelae of atherosclerosis, establishing plaque Mφ as important mediators of tissue damage and a potential target for prevention of AAA growth and rupture.
2025-03-06 | GSE284253 | GEO
Project description:There is no effective pharmacotherapy to prevent the growth and rupture of abdominal aortic aneurysms (AAA), a leading cause of death. We developed a novel preclinical model showing that the interaction of bona fide risk factors (i.e., cigarette smoke (CS) and hypercholesterolemia) induced AAA formation, rupture, and death. Elastin fragmentation resulted from CS-induced exacerbation of the atherosclerotic process, significant given atherosclerosis is a disease of the inner intimal layer of the artery, with the media remaining largely intact. Importantly, arterial injury was driven by CSF-1-dependent macrophages (Mφ) accumulating within developing atherosclerotic plaques that exhibited tissue degrading proteolytic activity in vivo. Single-cell RNA sequencing further demonstrated conservation of Mφ responses in atherosclerotic plaque from murine and human AAA. Our findings advance understanding of the pathological sequelae of atherosclerosis, establishing plaque Mφ as important mediators of tissue damage and a potential target for prevention of AAA growth and rupture.
2025-03-06 | GSE284249 | GEO
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.
2023-12-07 | GSE183464 | GEO
Project description:There is no effective pharmacotherapy to prevent the growth and rupture of abdominal aortic aneurysms (AAA), a leading cause of death. We developed a novel preclinical model showing that the interaction of bona fide risk factors (i.e., cigarette smoke (CS) and hypercholesterolemia) induced AAA formation, rupture, and death. Elastin fragmentation resulted from CS-induced exacerbation of the atherosclerotic process, significant given atherosclerosis is a disease of the inner intimal layer of the artery, with the media remaining largely intact. Importantly, arterial injury was driven by CSF-1-dependent macrophages (Mφ) accumulating within developing atherosclerotic plaques that exhibited tissue degrading proteolytic activity in vivo. Single-cell RNA sequencing further demonstrated conservation of Mφ responses in atherosclerotic plaque from murine and human AAA. Our findings advance understanding of the pathological sequelae of atherosclerosis, establishing plaque Mφ as important mediators of tissue damage and a potential target for prevention of AAA growth and rupture.
2025-03-06 | GSE284251 | GEO
Project description:Global gene expression information that can be used to identify pathways involved in the pathophysiology of disease. We used microarrays to identify which genes are expressed in either the abdominal aorta (control) or in abdominal aortic aneurysms (case), and also which genes may be differential between the two tissue states. Keywords: Characterization of expression in both diseased and non-diseased abdominal aortas.
2007-07-26 | GSE7084 | GEO
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-/-.
2025-10-29 | GSE280216 | GEO
Project description:Inflammation and elastin degradation are key hallmarks in the pathogenesis of abdominal aortic aneurysms (AAA). It has been acknowledged that activation of alpha7 nicotinic acetylcholine receptors (α7nAChRs) attenuates inflammation, termed the cholinergic anti-inflammatory pathway (CAP). Thus, we hypothesized that low-dose nicotine, an α7nAChR agonist, impairs the progression of AAAs in rats by activating the CAP. Male Sprague-Dawley rats underwent surgical AAA induction with intraluminal elastase infusion. We compared vehicle rats with rats treated with nicotine (1.25 mg/kg/day) and the aneurysm progression was monitored by weekly ultrasound images for 28 days. Nicotine significantly promoted AAA progression after 28 days of treatment (p=0.031). Additionally, gelatin zymography demonstrated that nicotine significantly reduced pro-matrix metalloprotease (pro-MMP) 2(p=0.029) and MMP9(p=0.030) activity in aneurysmal tissue. No significant difference was found in elastin content or the score of elastin degradation between the groups. Neither infiltrating neutrophils nor macrophages, nor aneurysmal messenger RNA (mRNA) levels of pro- or anti-inflammatory cytokines differed between the vehicle and nicotine group. Finally, no difference in mRNA levels of markers for antioxidative stress or vascular smooth muscle cells contractile phenotype was observed. However, proteomics analyses of non-aneurysmal abdominal aortas revealed that nicotine decreased proteins in the ontology terms inflammation and reactive oxygen species and in contradiction to augmented AAAs. In conclusion, treatment with the given nicotine dose augmented AAA progression in this rat model.
2023-07-20 | PXD040414 | Pride
Project description:A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.
2024-06-22 | GSE269845 | GEO