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.

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.