Inflammation and TGF-beta Signaling Differ between Abdominal Aneurysms and Occlusive Disease
| Autor: | K.M. van de Luijtgaarden, L Te Riet, H.J.M. Verhagen, Joyce Burger, I. van der Pluijm, Arne IJpma, P.M. van Heijningen, Ellen V. Rouwet, Jeroen Essers, Danielle Majoor-Krakauer |
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| Přispěvatelé: | Clinical Genetics, Pathology, Internal Medicine, Surgery, Molecular Genetics, Radiotherapy |
| Rok vydání: | 2019 |
| Předmět: |
lcsh:Diseases of the circulatory (Cardiovascular) system
Inflammation macromolecular substances Bone morphogenetic protein Bioinformatics environment and public health TGF-β signaling Article Gene expression occlusive disease gene expression profiling Medicine Pharmacology (medical) cardiovascular diseases General Pharmacology Toxicology and Pharmaceutics CXCL13 business.industry abdominal aneurysm Gene expression profiling enzymes and coenzymes (carbohydrates) lcsh:RC666-701 inflammation cardiovascular system Biomarker (medicine) medicine.symptom Signal transduction business Transforming growth factor |
| Zdroj: | Journal of Cardiovascular Development and Disease Volume 6 Issue 4 Journal of Cardiovascular Development and Disease, Vol 6, Iss 4, p 38 (2019) Journal of Cardiovascular Development and Disease, 6(4):38. Multidisciplinary Digital Publishing Institute (MDPI) |
| ISSN: | 2308-3425 |
| Popis: | 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 &beta (TGF-&beta ) signaling associated with AAA. Concluding our gene expression profiling approach identifies novel genes and an interplay between BMP and TGF-&beta signaling regulation specifically for AAA. |
| Databáze: | OpenAIRE |
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