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Influence of matrix metalloproteinase- 12 on fibrinogen level

Influence of matrix metalloproteinase- 12 on fibrinogen level
Influence of matrix metalloproteinase- 12 on fibrinogen level
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
matrixmetalloproteinase-12, fibrinogen, atherosclerosis, myocardial infarction
0021-9150
351-354
Motterle, Anna
d40cdfd5-322e-4d46-ab71-b8cb45732d84
Xiao, Qingzhong
de730b39-1e59-421e-a1e0-32e9b827036b
Kiechl, Stefan
2d181792-2823-4f3c-983d-c7e8a0fbeaf8
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Morris, Gareth E.
224069d7-bba1-4f7a-843e-73b278957b1a
Willeit, Johann
49fb46ff-991f-403f-9f24-c54d38a3a6bb
Caulfield, Mark J.
a13960ad-3f25-453e-a127-2913a935d73a
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab
Motterle, Anna
d40cdfd5-322e-4d46-ab71-b8cb45732d84
Xiao, Qingzhong
de730b39-1e59-421e-a1e0-32e9b827036b
Kiechl, Stefan
2d181792-2823-4f3c-983d-c7e8a0fbeaf8
Pender, Sylvia L.F.
62528b03-ec42-41bb-80fe-48454c2c5242
Morris, Gareth E.
224069d7-bba1-4f7a-843e-73b278957b1a
Willeit, Johann
49fb46ff-991f-403f-9f24-c54d38a3a6bb
Caulfield, Mark J.
a13960ad-3f25-453e-a127-2913a935d73a
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab

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).

Record type: Article

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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More information

e-pub ahead of print date: 11 November 2011
Published date: February 2012
Keywords: matrixmetalloproteinase-12, fibrinogen, atherosclerosis, myocardial infarction
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337475
URI: http://eprints.soton.ac.uk/id/eprint/337475
ISSN: 0021-9150
PURE UUID: 767075ac-84e1-406c-bca9-11cc6cbd91cd
ORCID for Sylvia L.F. Pender: ORCID iD orcid.org/0000-0001-6332-0333

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Date deposited: 26 Apr 2012 12:42
Last modified: 15 Mar 2024 03:08

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Contributors

Author: Anna Motterle
Author: Qingzhong Xiao
Author: Stefan Kiechl
Author: Gareth E. Morris
Author: Johann Willeit
Author: Mark J. Caulfield
Author: Shu Ye

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