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Cell Biology/Signaling

Role of Complement Cascade in Abdominal Aortic Aneurysms

Irene Hinterseher, Robert Erdman, Larry A. Donoso, Tamara R. Vrabec, Charles M. Schworer, John H. Lillvis, Amy M. Boddy, Kimberly Derr, Alicia Golden, William D. Bowen, Zoran Gatalica, Nikos Tapinos, James R. Elmore, David P. Franklin, John L. Gray, Robert P. Garvin, Glenn S. Gerhard, David J. Carey, Gerard Tromp, Helena Kuivaniemi
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https://doi.org/10.1161/ATVBAHA.111.227652
Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31:1653-1660
Originally published June 15, 2011
Irene Hinterseher
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Robert Erdman
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Larry A. Donoso
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Tamara R. Vrabec
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Charles M. Schworer
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John H. Lillvis
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Amy M. Boddy
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Kimberly Derr
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Alicia Golden
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William D. Bowen
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Zoran Gatalica
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Nikos Tapinos
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James R. Elmore
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David P. Franklin
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John L. Gray
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Robert P. Garvin
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Glenn S. Gerhard
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David J. Carey
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Gerard Tromp
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Helena Kuivaniemi
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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.

Conclusion—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.

  • aneurysms
  • gene expression
  • pathology
  • abdominal aortic aneurysm
  • complement cascade
  • Received December 6, 2010.
  • Accepted March 30, 2011.
  • © 2011 American Heart Association, Inc.
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    Role of Complement Cascade in Abdominal Aortic Aneurysms
    Irene Hinterseher, Robert Erdman, Larry A. Donoso, Tamara R. Vrabec, Charles M. Schworer, John H. Lillvis, Amy M. Boddy, Kimberly Derr, Alicia Golden, William D. Bowen, Zoran Gatalica, Nikos Tapinos, James R. Elmore, David P. Franklin, John L. Gray, Robert P. Garvin, Glenn S. Gerhard, David J. Carey, Gerard Tromp and Helena Kuivaniemi
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31:1653-1660, originally published June 15, 2011
    https://doi.org/10.1161/ATVBAHA.111.227652

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    Role of Complement Cascade in Abdominal Aortic Aneurysms
    Irene Hinterseher, Robert Erdman, Larry A. Donoso, Tamara R. Vrabec, Charles M. Schworer, John H. Lillvis, Amy M. Boddy, Kimberly Derr, Alicia Golden, William D. Bowen, Zoran Gatalica, Nikos Tapinos, James R. Elmore, David P. Franklin, John L. Gray, Robert P. Garvin, Glenn S. Gerhard, David J. Carey, Gerard Tromp and Helena Kuivaniemi
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31:1653-1660, originally published June 15, 2011
    https://doi.org/10.1161/ATVBAHA.111.227652
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