Influence of matrix metalloproteinase-12 on fibrinogen level

Anna Motterle1, Qingzhong Xiao, Stefan Kiechl

  • 1William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Atherosclerosis
|November 29, 2011
PubMed

Insights

Matrix metalloproteinase-12 (MMP12) influences fibrinogen levels. Lower MMP12 activity correlates with higher fibrinogen, increasing risks for atherosclerosis and myocardial infarction in humans.

Area of Science:

  • Cardiovascular Biology
  • Enzymology
  • Genetics

Background:

  • Matrix metalloproteinase-12 (MMP12) is known to degrade fibrinogen in vitro.
  • Elevated fibrinogen levels are associated with increased risk of advanced atherosclerosis and myocardial infarction.

Purpose of the Study:

  • To investigate the in vivo role of MMP12 in regulating plasma fibrinogen levels.
  • To examine the association between MMP12 genetic variation, fibrinogen levels, and cardiovascular disease risk in humans.

Main Methods:

  • MMP12 knockout mice were used to assess plasma fibrinogen levels compared to wildtype mice.
  • Differential allelic expression analysis of human MMP12 polymorphism rs17368582 was performed in vascular tissues.
  • A population cohort was analyzed to correlate MMP12 genotype with plasma fibrinogen, atherosclerosis, and myocardial infarction risk.

Main Results:

  • MMP12 knockout mice exhibited approximately 10-fold higher plasma fibrinogen levels than wildtype mice.
  • Human MMP12 polymorphism rs17368582 showed allele-specific expression, with the T allele having 1.6-fold higher expression than the C allele.
  • Individuals homozygous for the low-expression MMP12 allele had higher fibrinogen levels and significantly increased risks of advanced atherosclerosis and myocardial infarction.

Conclusions:

  • This study provides in vivo evidence in both mice and humans that MMP12 affects plasma fibrinogen levels.
  • MMP12 activity and its genetic variations are linked to fibrinogen regulation and cardiovascular disease risk.

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