Gene expression analysis of a porcine native abdominal aortic aneurysm model.

INTRODUCTION

We sought to characterize the gene expression patterns occurring during the development of aneurysms in the native porcine aorta.

METHODS

In Yorkshire swine, the infrarenal aorta was balloon dilated and infused with a solution of type I collagenase/pancreatic porcine elastase (16,000 U/1,000 U). Aneurysmal and control aortic samples were obtained at 1 (n = 3), 2 (n = 6), and 4 (n = 5) weeks following aneurysm induction. RNA was isolated, converted to biotin-modified antisense RNA and hybridized to porcine genome arrays. Aneurysmal and control gene intensities were compared using the 2-sample-for-means z-test. P < .01 was considered statistically significant.

RESULTS

Extracellular matrix remodeling genes that were upregulated in aneurysmal compared with control tissue included matrix metalloproteinase-1, -2, -3, and -9; MT-MMP; cathepsin-D, -H, -K, and -S; tissue inhibitor of metalloproteinase-1; and collagen I-alpha1 chain (P < .01). Elastin exhibited temporally downregulated gene expression (P < .01). Inflammatory genes that were upregulated included intercellular adhesion molecule-2, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-10, chemokine receptor-4, and tissue plasminogen activator (P < .01). Atherosclerosis and cancer genes that were upregulated included apolipoprotein E, acyl-CoA binding protein, friend leukemia virus integration-1, and E26 transformation-specific sequence (P < .01).

CONCLUSION

The porcine model replicates the gene expression patterns that are observed during the development of aneurysms in human studies as well as in rodent models. The porcine model thereby represents a novel method to study the impact of endovascular, cell-based, and other therapeutic interventions on AAA pathophysiology.