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Role of complement cascade in abdominal aortic aneurysms.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2011 Jul; Vol. 31 (7), pp. 1653-60. Date of Electronic Publication: 2011 Apr 14. - Publication Year :
- 2011
-
Abstract
- Objective: The goal of this study was to investigate the role of complement cascade genes in the pathobiology of human abdominal aortic aneurysms (AAAs).<br />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.<br />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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Aortic Aneurysm, Abdominal genetics
Binding Sites
Case-Control Studies
Chromatin Immunoprecipitation
Complement C2 analysis
Complement System Proteins genetics
Female
Gene Expression Profiling methods
Gene Expression Regulation
Genome-Wide Association Study
Humans
Immunohistochemistry
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Polymorphism, Genetic
Promoter Regions, Genetic
RNA, Messenger analysis
STAT5 Transcription Factor metabolism
Tumor Suppressor Proteins metabolism
Aortic Aneurysm, Abdominal immunology
Complement Activation genetics
Complement System Proteins analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 31
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 21493888
- Full Text :
- https://doi.org/10.1161/ATVBAHA.111.227652