Molecular Fingerprint for Terminal Abdominal Aortic Aneurysm Disease
| Autor: | Hendrik Bergert, Stefan A. Doderer, Irina Weinzierl, Gabor Gäbel, Stefan Ludwig, Irene Hinterseher, Wolfgang Wilfert, Jan H.N. Lindeman, Bernd H. Northoff, Daniel Teupser, Frank Schönleben, Lesca M. Holdt |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Genetic Markers
0301 basic medicine Pathology medicine.medical_specialty Angiogenesis Aortic Rupture endothelial cell differentiation Disease 030204 cardiovascular system & hematology Real-Time Polymerase Chain Reaction Molecular Fingerprint Vascular Medicine Endothelial cell differentiation gene microarray hypoxia-inducible factor 1 03 medical and health sciences angiogenesis 0302 clinical medicine abdominal aortic aneurysm Vascular Biology Predictive Value of Tests Risk Factors medicine Humans Gene Regulatory Networks Aorta Abdominal Cells Cultured Genetic Association Studies Original Research Oligonucleotide Array Sequence Analysis Gene Expression & Regulation business.industry Gene Expression Profiling Gene Microarray Fibroblasts Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Aneurysm Abdominal aortic aneurysm 030104 developmental biology Terminal (electronics) Transcriptome Cardiology and Cardiovascular Medicine business hypoxia‐inducible factor 1 Aortic Aneurysm Abdominal Signal Transduction |
| Zdroj: | Journal of the American Heart Association, 6(12) Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Popis: | Background Clinical 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 Results Aortic wall tissue specimens were collected during open elective (e AAA ; n=31) or emergency repair of ruptured AAA (r AAA ; 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 (e AAA : n=46; r AAA : 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 , ANGPTL 4 , LOX , SRPX 2 , FCGBP ), and a second set containing 5 genes exclusively upregulated in rAAA ( ADAMTS 9 , STC 1 , GFPT 2 , GAL 3 ST 4 , CCL 4L1 ). 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 r AAA versus e AAA shows enhanced microvessel density but also clear activation of the HIF ‐1α network in r AAA . Conclusions Our 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. |
| Databáze: | OpenAIRE |
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