Matrix metalloproteinase activity in thoracic aortic aneurysms associated with bicuspid and tricuspid aortic valves

Abstract

Objective Matrix metalloproteinases are endopeptidases that function in cell matrix turnover. Abnormal matrix metalloproteinase activity has been implicated in the formation of atherosclerotic abdominal aortic aneurysms. Recent studies suggest that abnormal matrix metalloproteinase activity may also be associated with the formation of atherosclerotic and nonatherosclerotic thoracic aortic aneurysms. Bicuspid aortic valves are associated with an intrinsic aortic pathology that predisposes to formation of proximal thoracic aneurysms while tricuspid aortic valves are not. The objective of this study was to compare the activities of matrix metalloproteinases and levels of their inhibitors in thoracic aneurysms of patients with bicuspid and tricuspid aortic valves. Methods Endogenous and total activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 were measured in proximal nonatherosclerotic thoracic aortic aneurysms of 16 patients with bicuspid aortic valves and 12 patients with tricuspid aortic valves. Levels of tissue inhibitor metalloproteinase-1 and -2 were also measured. Results were standardized to total protein (mg). Results Total matrix metalloproteinase-2 activity was greater in aneurysms associated with bicuspid valves when compared with those from tricuspid valves (43 ± 11 ng/mg vs 14 ± 2 ng/mg, P = .02). Total matrix metalloproteinase-9 activity was also greater in aneurysms associated with bicuspid aortic valves (4.0 ± 0.9 vs 1.5 ± 0.3, P = .02). There was no meaningful difference between groups in levels of tissue inhibitor-1 and -2. Conclusion The increased activity of matrix metalloproteinases in the walls of aneurysms associated with bicuspid aortic valves may partly explain the predilection to aneurysm formation in these patients.