Upregulation of matrix metalloproteinases and inflammatory mediators are associated with abdominal aortic aneurysm induction in a porcine model

Abstract

Gene expression was evaluated after induction of abdominal aortic aneurysm (AAA) in a porcine model. AAA were surgically induced in male Yorkshire swine by mechanical dilation and local perfusion with elastase/collagenase. RNA was isolated from AAA and normal aortic tissue at 4 hours and 10 days post induction. cDNA generated from the samples was hybridized to porcine gene chip arrays (20,201 genes), and expression was analyzed. Key matrix metalloproteinases, tissue inhibitors of metalloproteinases, and inflammatory cytokines associated with AAA pathogenesis were upregulated at 4 hours, but showed variable degrees of resolution or downregulation beneath baseline at 10 days (Table). Serine protease levels demonstrated significantly elevated expression throughout the 10 day interval. Mediators associated with the propagation of aneurysms in this porcine model can more clearly describe AAA formation and provide novel methods for the evaluation of effective endovascular treatment strategies. The persistence of such gene expression profiles at longer intervals may further characterize this model. Project funded by the American Vascular Association William J. von Liebig Award in conjunction with the NIH. Relative cDNA expression profiles of key gene products in AAA tissue samples