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

Autor:	IJpma A; Department of Clinical Genetics, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands. a.ijpma@erasmusmc.nl.; Department of Bioinformatics, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands. a.ijpma@erasmusmc.nl., Te Riet L; Department of Vascular Surgery, Erasmus University Medical Center, POB 2040 Rotterdam, The Netherlands. j.burger.1@erasmusmc.nl.; Department of Pharmacology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands. j.burger.1@erasmusmc.nl., van de Luijtgaarden KM; Department of Vascular Surgery, Erasmus University Medical Center, POB 2040 Rotterdam, The Netherlands. d.majoor-krakauer@erasmusmc.nl., van Heijningen PM; Department of Molecular Genetics, Cancer Genomics, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands. luukteriet@gmail.com., Burger J; Department of Clinical Genetics, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands. j.burger.1@erasmusmc.nl.; Department of Molecular Genetics, Cancer Genomics, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands. j.burger.1@erasmusmc.nl., Majoor-Krakauer D; Department of Clinical Genetics, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands. e.rouwet@erasmusmc.nl., Rouwet EV; Department of Vascular Surgery, Erasmus University Medical Center, POB 2040 Rotterdam, The Netherlands. j.essers@erasmusmc.nl., Essers J; Department of Vascular Surgery, Erasmus University Medical Center, POB 2040 Rotterdam, The Netherlands. j.essers@erasmusmc.nl.; Department of Molecular Genetics, Cancer Genomics, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands. j.essers@erasmusmc.nl.; Department of Radiation Oncology Erasmus University Medical Center, Rotterdam, The Netherlands. j.essers@erasmusmc.nl., Verhagen HJM; Department of Vascular Surgery, Erasmus University Medical Center, POB 2040 Rotterdam, The Netherlands. h.verhagen@erasmusmc.nl., van der Pluijm I; Department of Vascular Surgery, Erasmus University Medical Center, POB 2040 Rotterdam, The Netherlands. i.vanderpluijm@erasmusmc.nl.; Department of Molecular Genetics, Cancer Genomics, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands. i.vanderpluijm@erasmusmc.nl.
Jazyk:	angličtina
Zdroj:	Journal of cardiovascular development and disease [J Cardiovasc Dev Dis] 2019 Nov 01; Vol. 6 (4). Date of Electronic Publication: 2019 Nov 01.
DOI:	10.3390/jcdd6040038
Abstrakt:	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. Competing Interests: The authors declare no competing interests.
Databáze:	MEDLINE
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