Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valves

Abstract

Objective: The mechanisms contributing to ascending thoracic aortic aneurysms associated with bicuspid aortic valves may differ from ascending thoracic aortic aneurysms with tricuspid aortic valves. Matrix metalloproteinases and their endogenous inhibitors have been causally linked to ascending thoracic aortic aneurysm formation. This study tested the hypothesis that specific and different matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles would be observed in ascending thoracic aortic aneurysm samples from patients with bicuspid aortic valves versus tricuspid aortic valves.

Methods: Ascending thoracic aortic aneurysm samples taken from patients with bicuspid aortic valve (n = 53) and patients with tricuspid aortic valve (n = 46) were assessed for representative subtypes of all matrix metalloproteinase classes and all 4 known tissue inhibitors of metalloproteinases. Levels were compared [optical density units, median (interquartile range)] both to reference control ascending aortic samples (n = 26) and within each valve group by aneurysm diameter (< or =3.9 cm, 4.0-5.9 cm and > or =6.0 cm).

Results: Different and specific matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles were observed in the ascending thoracic aortic aneurysm groups. In bicuspid aortic valves, matrix metalloproteinase-2 increased by 34% when compared with either tricuspid aortic valves or control (P < .05), and matrix metalloproteinase-14 decreased by 59% compared with tricuspid aortic valves (P < .05). In tricuspid aortic valve samples, tissue inhibitors of metalloproteinase-2 decreased by 35% when compared with either tricuspid aortic valves or control (P < .05), and matrix metalloproteinase-13 increased by 140% in the 4.0- to 5.9-cm diameter range (P < .05).

Conclusions: A unique matrix metalloproteinase and tissue inhibitor of metalloproteinase portfolio was observed in ascending thoracic aortic aneurysms from patients with bicuspid aortic valve compared with patients with tricuspid aortic valve. These differences, suggesting disparate mechanisms of extracellular matrix remodeling, may provide unique biochemical targets for ascending thoracic aortic aneurysm prognostication and treatment in these 2 groups of patients.