ArticlesMatrix Metalloproteinase Expression in Nonrheumatic Aortic Stenosis
Section snippets
Tissue Acquisition and Preparation
Aortic valves were obtained at the time of surgery in nine male patients with aortic stenosis undergoing valve replacement at the Veterans Administration Medical Center, La Jolla, California. Additionally, aortic leaflets were obtained at the time of autopsy from four patients who died of noncardiac disease without aortic stenosis for comparison.
Preparation of the valve leaflets was as follows: sections for analysis were taken from a vertically orientated cut through the aortic cusps and sinus
Leaflet Architecture
Histologic analysis of the NAS valves demonstrated striking differences when compared with the aortic valves obtained from the control subjects, as seen in Table 1. All valves from patients with NAS demonstrated marked leaflet fibrosis and calcium deposition. The aortic valve leaflets obtained from the patients without a history of NAS exhibited neither of these characteristics. A hypercellular inflammatory infiltrate was present in 77% of the NAS specimens. None of the valve tissue from
Discussion
This study has demonstrated enhanced expression of MMP-1 (interstitial collagenase), MMP-2 (Gelatinase A), and MMP-3 (stromelysin) in aortic valves of patients with severe aortic stenosis. In addition, MMP-9 (gelatinase B) expression was documented exclusively in the valve leaflets of patients with aortic stenosis. Together, these metalloenzymes have the capability of degrading the collagenous and elastin components of the aortic valve. Importantly, activated MMP-3 can also activate MMP-1 and
Conclusion
In conclusion, the findings reported in this study confirm the presence of an inflammatory infiltrate composed of macrophages and lymphocytes in association with NAS. Additionally, using immunohistochemical techniques, the presence of increased expression of MMP-1, -2, and -3 and the unique expression of MMP-9 in NAS valve leaflets was documented. These findings are consistent with the hypothesis that NAS is an active process associated with chronic inflammation. The presence of MMPs within the
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