Periodontal diseases may increase risk of vascular calcification in cardiovascular diseases but the potential mechanisms are not defined. Fetuin, a naturally-occurring serum glycoprotein in humans, protects against ectopic arterial calcification. We considered that patients with periodontitis could be at increased risk of developing calcifying atheromas because periodontal-disease associated enzymes may enter the circulation and subsequently degrade fetuin, thereby disrupting its ability to inhibit calcification. By in silico investigation, MMP -3 and -7 were predicted to cleave fetuin but only MMP-7 actually degraded human fetuin in vitro. MMP-7 degradation of fetuin was time- and concentration- dependent and was inhibited by an MMP Inhibitor. By mass spectrometry the presence of novel, MMP-7-mediated cleavage sites in fetuin were found. Fetuin bound tightly to MMP-7 (kd =2.96 x 10-9 M). The degradation of fetuin by MMP-7 could explain, at least in part, the apparent association between periodontal diseases and calcifying atheromas.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/42911 |
| Date | 27 November 2013 |
| Creators | Schure, Ryan Samuel |
| Contributors | McCulloch, Christopher, Tenenbaum, Howard |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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