Abstract 14357: A Reproducible Porcine Model of Thoracic Aortic Aneurysm
Objective: Thoracic aortic aneurysms (TAAs) develop secondary to abnormal aortic extracellular matrix (ECM) remodeling, resulting in a weakened and dilated aortic wall that can progress to rupture if left unattended. Currently, no diagnostic/prognostic tests are available for detection of TAA disease. This is largely driven by the lack of large animal models which permit serial blood sampling and correlation to changes within the aortic tissue harvested at intermediate times during TAA development. The objective of the current study was to establish a reproducible porcine model of aortic dilation progressing to TAA.
Methods: Descending TAAs were induced in Yorkshire pigs (20-25kg; n=7) through intra-adventitial injections of type II bacterial collagenase (5mls, 0.35mg/ml) and peri-adventitial exposure to 0.5g CaCl2 powder. Three weeks post-TAA induction, aortas were harvested and tissue was collected for biochemistry (matrix metalloproteinases (MMPs) and inhibitors (TIMPs)), histology (architectural changes), and aortic size determination. A subset of animals underwent magnetic resonance imaging pre-operatively and at terminal surgery. TAA-induced animals were compared to sham-operated controls (n=6).
Results: Three weeks post-TAA induction, aortic diameter increased 38±13% as compared to controls (Figure; p<0.05). Histological changes within the aortic wall were characterized by decreased collagen content and elastic lamellar degradation. The protein abundance of MMP-3, -8, -9, and -12 increased in TAA tissue homogenates as compared to controls, while TIMP-1, and -4 decreased (Figure; *p<0.05).
Conclusions: These data demonstrate aortic dilation, aortic medial degeneration, and alterations in MMP/TIMP abundance, which is consistent with TAA formation. This large animal model, recapitulating the hallmarks of human TAAs, will provide a reproducible test bed for diagnostic, prognostic, and therapeutic approaches for this disease.
- © 2012 by American Heart Association, Inc.