Microarray-based Gene Expression Profiling of Abdominal Aortic Aneurysm

Butt, H.Z.; Sylvius, Nicolas; Salem, M.K.; Wild, John B.; Dattani, Nikesh; Sayers, Robert D.; Bown, Matthew J.

doi:10.1016/j.ejvs.2016.03.016

Cited by 22 publications

(22 citation statements)

References 21 publications

(6 reference statements)

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“…However, the significance of increased hs-CRP in already established aneurysms is unknown, as inflammation is a multifactorial process. Similar to what we find, other studies reported the role of the immune-related genes and pathways in AOD and AAA disease [55][56][57][58]. In the present study, however, we directly compared AAA and AOD instead of comparing both to a control group, which eliminates all genes that they have in common, or are similarly up-or downregulated.…”

Section: Discussionsupporting

confidence: 65%

Inflammation and TGF-β Signaling Differ between Abdominal Aneurysms and Occlusive Disease

IJpma

Riet

Luijtgaarden

et al. 2019

JCDD

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Abdominal aortic aneurysms (AAA), are usually asymptomatic until rupture causes fatal bleeding, posing a major vascular health problem. AAAs are associated with advanced age, male gender, and cardiovascular risk factors (e.g. hypertension and smoking). Strikingly, AAA and AOD (arterial occlusive disease) patients have a similar atherosclerotic burden, yet develop either arterial dilatation or occlusion, respectively. The molecular mechanisms underlying this diversion are yet unknown. As this knowledge could improve AAA treatment strategies, we aimed to identify genes and signaling pathways involved. We compared RNA expression profiles of abdominal aortic AAA and AOD patient samples. Based on differential gene expression profiles, we selected a gene set that could serve as blood biomarker or as pharmacological intervention target for AAA. In this AAA gene list we identified previously AAA-associated genes COL11A1, ADIPOQ, and LPL, thus validating our approach as well as novel genes; CXCL13, SLC7A5, FDC-SP not previously linked to aneurysmal disease. Pathway analysis revealed overrepresentation of significantly altered immune-related pathways between AAA and AOD. Additionally, we found bone morphogenetic protein (BMP) signaling inhibition simultaneous with activation of transforming growth factor β (TGF-β) signaling associated with AAA. Concluding our gene expression profiling approach identifies novel genes and an interplay between BMP and TGF-β signaling regulation specifically for AAA.

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Section: Discussionsupporting

confidence: 65%

Inflammation and TGF-β Signaling Differ between Abdominal Aneurysms and Occlusive Disease

IJpma

Riet

Luijtgaarden

et al. 2019

JCDD

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“…There have been a few earlier investigations with different study designs using gene expression array analyses from AAA patients, but this is the first study using whole genome microarrays to compare relative mRNA expression patterns between stable and ruptured AAAs in order to identify processes associated with AAA progression and rupture. With our approach we were able to identified and validate 2 gene sets.…”

Section: Discussionmentioning

confidence: 99%

Molecular Fingerprint for Terminal Abdominal Aortic Aneurysm Disease

Gäbel

Northoff

Weinzierl

et al. 2017

JAHA

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BackgroundClinical decision making in abdominal aortic aneurysms (AAA) relies completely on diameter. At this point, improved decision tools remain an unmet medical need. Our goal was to identify changes at the molecular level specifically leading up to AAA rupture.Methods and ResultsAortic wall tissue specimens were collected during open elective (eAAA; n=31) or emergency repair of ruptured AAA (rAAA; n=17), and gene expression was investigated using microarrays. Identified candidate genes were validated with quantitative real‐time polymerase chain reaction in an independent sample set (eAAA: n=46; rAAA: n=18). Two gene sets were identified, 1 set containing 5 genes linked to terminal progression, that is, positively associated with progression of larger AAA, and with rupture (HILPDA,ANGPTL4,LOX,SRPX2,FCGBP), and a second set containing 5 genes exclusively upregulated in rAAA (ADAMTS9,STC1,GFPT2,GAL3ST4,CCL4L1). Genes in both sets essentially associated with processes related to impaired tissue remodeling, such as angiogenesis and adipogenesis. In gene expression experiments we were able to show that upregulated gene expression for identified candidate genes is unique for AAA. Functionally, the selected upregulated factors converge at processes coordinated by the canonical HIF‐1α signaling pathway and are highly expressed in fibroblasts but not inflammatory cells of the aneurysmatic wall. Histological quantification of angiogenesis and exploration of the HIF‐1α network in rAAA versus eAAA shows enhanced microvessel density but also clear activation of the HIF‐1α network in rAAA.ConclusionsOur study shows a specific molecular fingerprint for terminal AAA disease. These changes appear to converge at activation of HIF‐1α signaling in mesenchymal cells. Aspects of this cascade might represent targets for rupture risk assessment.

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“…Abdominal aortic aneurysms (AAAs) are life-threatening diseases that are defined as an abdominal aorta with a diameter > 3 cm or larger than normal [1,2]. This condition occurs with atherosclerosis or plaque build-up, which weakens the walls of the abdominal aorta and results in an outward bulge, similar to a balloon.…”

Section: Introductionmentioning

confidence: 99%

Detection of microRNA-335-5p on an Interdigitated Electrode Surface for Determination of the Severity of Abdominal Aortic Aneurysms

Liu

Wang

et al. 2020

Nanoscale Res Lett

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Abdominal aortic aneurysm (AAA) refers to the enlargement of the lower artery of the abdominal aorta, and identification of an early detection tool is urgently needed for diagnosis. In the current study, an interdigitated electrode (IDE) sensing surface was used to identify miRNA-335-5p, which reflects the formation of AAAs. The uniformity of the silica material was observed by 3D profilometry, and the chemically modified highly conductive surface improved the detection via the I-V mode. The targeted miRNA-335-5p was detected in a dose-dependent manner and based on linear regression and 3σ analyses, the sensitivity was determined to be 1 fM with a biotinylated probe. The high specificity was shown by discriminating the target sequence from noncomplementary and single-and triple-mismatched sequences. These outputs demonstrated the high-performance detection of miRNA-335-5p with good reproducibility for determination of the severity of AAA.

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Microarray-based Gene Expression Profiling of Abdominal Aortic Aneurysm

Cited by 22 publications

References 21 publications

Inflammation and TGF-β Signaling Differ between Abdominal Aneurysms and Occlusive Disease

Inflammation and TGF-β Signaling Differ between Abdominal Aneurysms and Occlusive Disease

Molecular Fingerprint for Terminal Abdominal Aortic Aneurysm Disease

Detection of microRNA-335-5p on an Interdigitated Electrode Surface for Determination of the Severity of Abdominal Aortic Aneurysms

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