title: Influence of matrix metalloproteinase-12 on fibrinogen level.
abstract: In vitro studies have shown that matrix metalloproteinase-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 fibrinogen level 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 fibrinogen levels (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 fibrinogen level.
authors: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors: Anna
authors: A
authors: Motterle
authors: Qingzhong
authors: Q
authors: Xiao
authors: Stefan
authors: S
authors: Kiechl
authors: Sylvia L F
authors: SL
authors: Pender
authors: Gareth E
authors: GE
authors: Morris
authors: Johann
authors: J
authors: Willeit
authors: Mark J
authors: MJ
authors: Caulfield
authors: Shu
authors: S
authors: Ye
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology / Q000235:genetics; D004739:England; D005340:Fibrinogen / Q000378:metabolism*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007558:Italy; D016014:Linear Models; D015810:Linkage Disequilibrium; D016015:Logistic Models; D053508:Matrix Metalloproteinase 12 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D005340:Fibrinogen; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12