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Murine Surgical Model of Topical Elastase Induced Descending Thoracic Aortic Aneurysm
Published on: August 24, 2019
Temporal changes in mouse aortic wall gene expression during the development of elastase-induced abdominal aortic
Sarah J Van Vickle-Chavez1, William S Tung, Tarek S Absi
1Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Journal of Vascular Surgery
|May 9, 2006
Summary
Experimental abdominal aortic aneurysms in mice show significant gene expression changes in the aortic wall. These alterations involve inflammation, matrix degradation, and tissue remodeling, offering insights into aneurysm development.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Genomics
Background:
- Abdominal aortic aneurysms (AAAs) are life-threatening vascular diseases characterized by aortic wall dilation and rupture.
- The molecular mechanisms underlying AAA pathogenesis, particularly early gene expression changes, remain incompletely understood.
Purpose of the Study:
- To comprehensively characterize temporal gene expression profiles in the mouse aortic wall during the development of experimental AAAs.
- To identify key genes and pathways involved in the inflammatory and remodeling processes associated with AAA formation.
Main Methods:
- Experimental AAAs were induced in C57BL/6 mice using elastase perfusion.
- Aortic wall gene expression was analyzed using nylon microarrays at multiple time points (0, 3, 7, 10, and 14 days) post-perfusion.
- Gene expression data were normalized using z scores and analyzed for significant differences between experimental and control groups.
Main Results:
- Elastase perfusion led to progressive aortic dilation, inflammation, and medial remodeling, consistent with AAA development.
- A significant number of genes (336) showed altered expression post-elastase perfusion, with notable upregulation of inflammatory and matrix-degrading enzymes (e.g., interleukin-6, gelatinase B/matrix metalloproteinase-9).
- Direct comparison revealed 384 differentially expressed genes, including upregulated genes involved in MAPK signaling and inflammatory responses, and downregulated genes related to coagulation and apoptosis.
Conclusions:
- Elastase-induced AAA development in mice is associated with dynamic changes in aortic wall gene expression, reflecting acute and chronic inflammation, matrix degradation, and vascular remodeling.
- These identified gene expression alterations provide a foundation for further research into the molecular mechanisms driving aneurysmal degeneration.
