OBJECTIVE: The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs). METHODS AND RESULTS: Results of a genome-wide microarray expression profiling revealed 3274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were significantly differentially expressed between AAA and the controls. In silico analysis of the promoters of the 13 complement cascade genes showed enrichment for transcription factor binding sites for signal transducer and activator of transcription (STAT)5A. Chromatin-immunoprecipitation experiments demonstrated binding of transcription factor STAT5A to the promoters of the majority of the complement cascade genes. Immunohistochemical analysis showed strong staining for C2 in AAA tissues. CONCLUSIONS: These results provide strong evidence that the complement cascade plays a role in human AAA. Based on our microarray studies, the pathway is activated in AAA, particularly via the lectin and classical pathways. The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression.
OBJECTIVE: The goal of this study was to investigate the role of complement cascade genes in the pathobiology of humanabdominal aortic aneurysms (AAAs). METHODS AND RESULTS: Results of a genome-wide microarray expression profiling revealed 3274 differentially expressed genes between aneurysmal and control aortic tissue. Interestingly, 13 genes in the complement cascade were significantly differentially expressed between AAA and the controls. In silico analysis of the promoters of the 13 complement cascade genes showed enrichment for transcription factor binding sites for signal transducer and activator of transcription (STAT)5A. Chromatin-immunoprecipitation experiments demonstrated binding of transcription factor STAT5A to the promoters of the majority of the complement cascade genes. Immunohistochemical analysis showed strong staining for C2 in AAA tissues. CONCLUSIONS: These results provide strong evidence that the complement cascade plays a role in humanAAA. Based on our microarray studies, the pathway is activated in AAA, particularly via the lectin and classical pathways. The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression.
Authors: Stephen A Badger; Chee V Soong; Mark E O'Donnell; Caroline Mercer; Ian S Young; Anne E Hughes Journal: J Vasc Surg Date: 2008-10-01 Impact factor: 4.268
Authors: Gerard Tromp; Zoran Gatalica; Magdalena Skunca; Ramon Berguer; Thomas Siegel; Ronald A Kline; Helena Kuivaniemi Journal: Ann Vasc Surg Date: 2004-07 Impact factor: 1.466
Authors: Hui-Fang Zhou; Huimin Yan; Cordula M Stover; Tamara Montes Fernandez; Santiago Rodriguez de Cordoba; Wen-Chao Song; Xiaobo Wu; Robert W Thompson; Wilhelm J Schwaeble; John P Atkinson; Dennis E Hourcade; Christine T N Pham Journal: Proc Natl Acad Sci U S A Date: 2012-01-30 Impact factor: 11.205
Authors: Helena Kuivaniemi; Natzi Sakalihasan; Frank A Lederle; Gregory T Jones; Jean-Olivier Defraigne; Nicos Labropoulos; Victor Legrand; Jean-Baptiste Michel; Christoph Nienaber; Marc A Radermecker; John A Elefteriades Journal: Aorta (Stamford) Date: 2013-06-01
Authors: Hui-fang Zhou; Huimin Yan; Paula Bertram; Ying Hu; Luke E Springer; Robert W Thompson; John A Curci; Dennis E Hourcade; Christine T N Pham Journal: Proc Natl Acad Sci U S A Date: 2013-10-28 Impact factor: 11.205
Authors: Matthew C Pahl; Kimberly Derr; Gabor Gäbel; Irene Hinterseher; James R Elmore; Charles M Schworer; Thomas C Peeler; David P Franklin; John L Gray; David J Carey; Gerard Tromp; Helena Kuivaniemi Journal: BMC Med Genomics Date: 2012-06-15 Impact factor: 3.063
Authors: I Hinterseher; G Gäbel; F Corvinus; C Lück; H D Saeger; H Bergert; G Tromp; H Kuivaniemi Journal: Eur J Clin Microbiol Infect Dis Date: 2011-08-13 Impact factor: 3.267
Authors: Evan J Ryer; Kaitryn E Ronning; Robert Erdman; Charles M Schworer; James R Elmore; Thomas C Peeler; Christopher D Nevius; John H Lillvis; Robert P Garvin; David P Franklin; Helena Kuivaniemi; Gerard Tromp Journal: Int J Mol Sci Date: 2015-05-18 Impact factor: 5.923
Authors: Matthew C Pahl; Robert Erdman; Helena Kuivaniemi; John H Lillvis; James R Elmore; Gerard Tromp Journal: Int J Mol Sci Date: 2015-05-18 Impact factor: 5.923
Authors: Irene Hinterseher; Charles M Schworer; John H Lillvis; Elizabeth Stahl; Robert Erdman; Zoran Gatalica; Gerard Tromp; Helena Kuivaniemi Journal: Int J Mol Sci Date: 2015-05-18 Impact factor: 5.923