Article
Identification and investigation of genes implicated in abdominal aortic aneurysms
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Authors
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Irene Hinterseher
- Weis Center for Research, Geisinger Health System, Danville, PA
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Robert Erdman
- Weis Center for Research, Geisinger Health System, Danville, PA
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Kimberly Kerr
- Weis Center for Research, Geisinger Health System, Danville, PA
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Alicia Golden
- Weis Center for Research, Geisinger Health System, Danville, PA
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Matthew Cindric
- Weis Center for Research, Geisinger Health System, Danville, PA
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Charles Schworer
- Weis Center for Research, Geisinger Health System, Danville, PA
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Gabor Gäbel
- University Hospital Carl Gustav Carus, Departement of Visceral, Thoracic and Vascular Surgery, Dresden
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Hendrik Bergert
- University Hospital Carl Gustav Carus, Departement of Visceral, Thoracic and Vascular Surgery, Dresden
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Hans Detlev Saeger
- Universitätsklinikum Carl Gustav Carus der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden
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James Elmore
- Weis Center for Research, Geisinger Health System, Danville, PA
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David Franklin
- Weis Center for Research, Geisinger Health System, Danville, PA
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David Carey
- Weis Center for Research, Geisinger Health System, Danville, PA
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Gerardus Tromp
- Weis Center for Research, Geisinger Health System, Danville, PA
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Helena Kuivaniemi
- Weis Center for Research, Geisinger Health System, Danville, PA
| Published: | May 20, 2011 |
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Outline
Text
Introduction: Abdominal Aortic Aneurysms (AAA) are known to be influenced by environmental and genetic factors. The pathophysiology of AAA is characterized by degradation of extracellular matrix, loss of elastin and vascular smooth muscle cells, and local chronic inflammation. The goal of the current study was to identify the most common genes involved in development of AAA using the commonality of two different microarray systems. Further investigation of promising genes was performed.
Materials and methods: Affymetrix microarrays were used to analyze total RNA isolated from 4 AAAs and 4 control aortic tissues. Statistical comparison with previously published analysis using Illumina arrays on an independant set of aortic tissue samples was performed. Biological pathways were analysed for genes that were common between the two data sets, for selected genes Western Blot, Immunohistochemistry and RT-PCR were performed.
Results: A total of 57 genes have statistically significant differential expression in both studies. Fisher’s exact test: p<2.2e-16; OR=8.92 (95% CI: 5.64–14.33). Pathway analysis showed that 13 genes were associated with inflammation and 9 were involved with calcium metabolism. Another group were genes of cell differentiation and adhesion. We selected the following genes of
- calcium metabolism: NPTX2, PTPRC,
- cell development and differentiation: CD4, GATM, LAMA2,
- cell adhesion: ITGA10, ITGA5.
Western blotting and Immunohistochemistry confirmed, with exception of NPTX2, significantly different results between AAA and controls on protein level. The results from RT-PCR confirmed the significant differences of the expression data for NPTX2, CD4, GATM und ITGA10.
Conclusion: 57 genes were differentially expressed in AAA using two different microarray methods and two different sets of samples. New biological pathway possibilities as altered calcium metablism or changes in cell differentiation and development were detected. First follow-up of 7 selected genes confirmed for 6 the expression results on protein level and 4 genes with RT-PCR.
