Dataset Information

Inflammation and TGF-? Signaling Differ between Abdominal Aneurysms and Occlusive Disease.

ABSTRACT: 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 ? (TGF-?) signaling associated with AAA. Concluding our gene expression profiling approach identifies novel genes and an interplay between BMP and TGF-? signaling regulation specifically for AAA.

SUBMITTER: IJpma A

PROVIDER: S-EPMC6955744 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

IJpma A A Te Riet L L van de Luijtgaarden K M KM van Heijningen P M PM Burger J J Majoor-Krakauer D D Rouwet E V EV Essers J J Verhagen H J M HJM van der Pluijm I I

Journal of cardiovascular development and disease 20191101 4

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 kno ...[more]

PMID: 31683995

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Project description:Abdominal aortic aneurysm (AAA) is a prevalent cardiovascular disease characterized by the focal dilation of the aorta, which supplies blood to all the organs and tissues in the systemic circulation. With the AAA increasing in diameter over time, the risk of aneurysm rupture is generally associated with the size of the aneurysm. If diagnosed on time, intervention is recommended to prevent AAA rupture. The criterion to decide on surgical intervention is determined by measuring the maximum diameter of the aneurysm relative to the critical value of 5.5 cm. However, a more reliable approach could be based on understanding the biomechanical behavior of the aneurysmal wall. In addition, geometric features that are proven to be significant predictors of the AAA wall mechanics could be used as surrogates of the AAA biomechanical behavior and, subsequently, of the aneurysm's risk of rupture. The aim of this work is to identify those geometric indices that have a high correlation with AAA wall stress in the population of patients who received an emergent repair of their aneurysm. In-house segmentation and meshing algorithms were used to model 75 AAAs followed by estimation of the spatially distributed wall stress by performing finite element analysis. Fifty-two shape and size geometric indices were calculated for the same models using MATLAB scripting. Hypotheses testing were carried out to identify the indices significantly correlated with wall stress by constructing a Pearson's correlation coefficient matrix. The analyses revealed that 12 indices displayed high correlation with the wall stress, amongst which wall thickness and curvature-based indices exhibited the highest correlations. Stepwise regression analysis of these correlated indices indicated that wall stress can be predicted by the following four indices with an accuracy of 76%: maximum aneurysm diameter, aneurysm sac length, average wall thickness at the maximum diameter cross-section, and the median of the wall thickness variance. The primary outcome of this work emphasizes the use of global measures of size and wall thickness as geometric surrogates of wall stress for emergently repaired AAAs.

Dataset Information

Inflammation and TGF-? Signaling Differ between Abdominal Aneurysms and Occlusive Disease.

Publications

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

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