Abstract 513: Role of Membrane-Type 1 Matrix Metalloproteinase in the Pathogenesis of Thoracic Aortic Aneurysms
Background The histopathologic hallmark of thoracic aortic aneurysms (TAAs) is medial degeneration with extensive loss of elastic lamellar proteins, including fibrillin-1 (Fbn-1). TAA in Marfan Syndrome is associated with Fbn-1 mutations. Fbn-1 is degraded by membrane-type 1 matrix metalloproteinase (MT1-MMP) in vitro. While elevated levels of MT1-MMP have been associated with TAA, its effect on Fbn-1 in TAA is unknown.
Objectives We attempted to characterize tissue MT1-MMP and Fbn-1 in normal and TAA patients (non-Marfan) to determine if Fbn-1 degradation is correlated with elevated MT1-MMP levels.
Methods MT1-MMP and Fbn-1 levels were measured in TAA tissue from patients undergoing repair and in control aorta (CON) from patients undergoing coronary artery bypass grafting. Specimens were homogenized, protein was extracted and quantified, and the extracts were analyzed by Western blotting with antibodies to human MT1-MMP and Fbn-1.
Results Elevated levels of MT1-MMP were detected in 11/13 TAA, while 4/6 CON had undetectable levels (p < 0.02) (Fig. 1a). In preliminary subset analysis, Fbn-1 degradation products were detected in 2 TAA samples with high levels of MT1-MMP but no detectable Fbn-1 degradation products were found in 2 CON samples that showed low levels of MT1-MMP (Fig. 1b).
Conclusions Elevated levels of MT1-MMP were associated with Fbn-1 degradation, this may represent a pathologic mechanism of TAA formation.
- © 2013 by American Heart Association, Inc.