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Open AccessArticle

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

1
Department of Clinical Genetics, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
2
Department of Bioinformatics, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
3
Department of Vascular Surgery, Erasmus University Medical Center, POB 2040 Rotterdam, The Netherlands
4
Department of Pharmacology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
5
Department of Molecular Genetics, Cancer Genomics, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
6
Department of Radiation Oncology Erasmus University Medical Center, Rotterdam, The Netherlands
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Cardiovasc. Dev. Dis. 2019, 6(4), 38; https://doi.org/10.3390/jcdd6040038
Received: 16 September 2019 / Revised: 17 October 2019 / Accepted: 29 October 2019 / Published: 1 November 2019
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.
Keywords: abdominal aneurysm; occlusive disease; gene expression profiling; inflammation; TGF-β signaling abdominal aneurysm; occlusive disease; gene expression profiling; inflammation; TGF-β signaling
MDPI and ACS Style

IJpma, A.; te Riet, L.; van de Luijtgaarden, K.M.; van Heijningen, P.M.; Burger, J.; Majoor-Krakauer, D.; Rouwet, E.V.; Essers, J.; Verhagen, H.J.M.; van der Pluijm, I. Inflammation and TGF-β Signaling Differ between Abdominal Aneurysms and Occlusive Disease. J. Cardiovasc. Dev. Dis. 2019, 6, 38.

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