Role of complement cascade in abdominal aortic aneurysms

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).

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.

Figure 1

Modified “Complement and coagulation cascades” (hsa04610) pathway from KEGG. Only the complement cascade part of the pathway is shown. Protein symbols were replaced by gene symbols to reflect gene-centric data. See key for explanation of colors and symbols. Supplemental Table II and Supplemental Figure I provide details on the results.

Figure 2

Immunohistochemical staining for C2, C3 (α-chain), CFH, and STAT5A in the adventitia and media of AAA tissue and control aortic tissue. Scale bar = 50 µm.

Figure 3

Immunohistochemical images of a lymph node, a thrombus, neovessels and nerve or ganglion cells in AAA tissue. Antibodies against C2, C3 (α-chain), CFH, and STAT5A were used for staining. Scale bar = 50 µm.