Influence of matrix metalloproteinase- 12 on fibrinogen level

Motterle, Anna, Xiao, Qingzhong, Kiechl, Stefan, Pender, Sylvia L.F., Morris, Gareth E., Willeit, Johann, Caulfield, Mark J. and Ye, Shu (2012) Influence of matrix metalloproteinase- 12 on fibrinogen level. Atherosclerosis, 220 (2), 351-354. (doi:10.1016/j.atherosclerosis.2011.11.003).

Abstract

In vitro studies have shown that matrixmetalloproteinase-12 (MMP12) can degrade fibrinogen, a clotting factor whose level predicts risk of advanced atherosclerosis and myocardial infarction. In this study, we found that mean plasma fibrinogenlevel was approximately 10-fold higher in MMP12 knockout mice than wildtype mice (p = 0.0006). Differential allelic expression analysis of human MMP12 gene polymorphism rs17368582 in human vascular tissues showed an allele-specific effect on MMP12 expression, with one allele (T) having 1.6 fold higher expression level than the other allele (C) (p = 0.0006). In a population cohort, we found that individuals homozygous for the MMP12 low expression allele had higher plasma fibrinogenlevels (2.95 mg/mL compared with 2.61 mg/mL in other individuals, p = 0.029) and increased risk of advanced atherosclerosis [odds ratio 6.3 (95% CI 1.9–20.8), p = 0.003] and myocardial infarction [hazard ratio 5.6 (95% CI 1.7–18.3), p = 0.005]. In summary, our study in mouse and humans provides in vivo evidence of an effect of MMP12 on fibrinogenlevel

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Contributors

Author: Sylvia L.F. Pender

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