Novel pathways in the pathobiology of human abdominal aortic aneurysms
Autor: | Matthew C Pahl, David P. Franklin, Irene Hinterseher, Elizabeth C. Stahl, James R. Elmore, John L. Gray, David J. Carey, William D. Bowen, Matthew C. Cindric, Robert Erdman, Zoran Gatalica, Kimberly Derr, Alicia Golden, Helena Kuivaniemi, Gerard Tromp, John H Lillvis, Robert P. Garvin, Kathryn L. Jackson, Michael A. Chernousov, Charles M. Schworer |
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Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
Male
Pathology medicine.medical_specialty Microarray Down-Regulation macromolecular substances PTPRC Bioinformatics Article Antibodies Pathology and Forensic Medicine Receptor Activity-Modifying Protein 1 Pathogenesis Aortic aneurysm medicine Cell Adhesion Humans Gene Regulatory Networks cardiovascular diseases Aorta Abdominal Calcium Signaling RNA Messenger Molecular Biology Gene Aged Oligonucleotide Array Sequence Analysis Regulation of gene expression Inflammation biology NADPH Oxidases Cell Differentiation Cell Biology General Medicine medicine.disease Abdominal aortic aneurysm Up-Regulation Gene Expression Regulation cardiovascular system biology.protein FOSB Aortic Aneurysm Abdominal |
Popis: | Objectives: Abdominal aortic aneurysm (AAA), a dilatation of the infrarenal aorta, typically affects males >65 years. The pathobiological mechanisms of human AAA are poorly understood. The goal of this study was to identify novel pathways involved in the development of AAAs. Methods: A custom-designed ‘AAA-chip’ was used to assay 43 of the differentially expressed genes identified in a previously published microarray study between AAA (n = 15) and control (n = 15) infrarenal abdominal aorta. Protein analyses were performed on selected genes. Results: Altogether 38 of the 43 genes on the ‘AAA-chip’ showed significantly different expression. Novel validated genes in AAA pathobiology included ADCY7, ARL4C, BLNK, FOSB, GATM, LYZ, MFGE8, PRUNE2, PTPRC, SMTN, TMODI and TPM2. These genes represent a wide range of biological functions, such as calcium signaling, development and differentiation, as well as cell adhesion not previously implicated in AAA pathobiology. Protein analyses for GATM, CD4, CXCR4, BLNK, PLEK, LYZ, FOSB, DUSP6, ITGA5 and PTPRC confirmed the mRNA findings. Conclusion: The results provide new directions for future research into AAA pathogenesis to study the role of novel genes confirmed here. New treatments and diagnostic tools for AAA could potentially be identified by studying these novel pathways. |
Databáze: | OpenAIRE |
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