Matrix Metalloproteinase Mediated Type I Collagen Degradation - An Independent Risk Factor for Mortality in Women.
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major role in this matter. C1M is a biomarker measuring type I collagen degradation fragments in blood. The aim of the current study was to investigate whether MMP mediated type I collagen degradation (C1M) was predictive of mortality in a large prospective cohort of Danish women aged 48-89 (n = 5855). Subjects with high serum C1M showed significant increased mortality. The adjusted three year HR was 2.02 [95% CI: 1.48-2.76] for all-cause mortality, 2.32 [95% CI: 1.51-3.56] for cancer and 1.77 [95% CI: 0.98-3.17] for cardiovascular diseases. The adjusted nine year HR was 1.50 [95% CI: 1.28-1.75] for all-cause mortality, 1.49 [95% CI: 1.16-1.90] for cancer and 1.69 [95% CI: 1.27-2.24] for cardiovascular diseases. High MMP-mediated type I collagen degradation was associated with increased mortality. Subjects with high C1M had a 2-fold increase in mortality compared to subjects with low levels of this collagen degradation product.
Nordic Bioscience A/S, Herlev, Denmark.
K
K
Dragsbæk
Nordic Bioscience A/S, Herlev, Denmark.
J S
JS
Neergaard
Nordic Bioscience A/S, Herlev, Denmark.
H B
HB
Hansen
Nordic Bioscience A/S, Herlev, Denmark.
I
I
Byrjalsen
Center for Clinical and Basic Research, Vejle, Denmark.
P
P
Alexandersen
Nordic Bioscience A/S, Herlev, Denmark.
S N
SN
Kehlet
Nordic Bioscience A/S, Herlev, Denmark.
A-C
AC
Bay-Jensen
Nordic Bioscience A/S, Herlev, Denmark.
C
C
Christiansen
Nordic Bioscience A/S, Herlev, Denmark.
M A
MA
Karsdal
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D024042:Collagen Type I / Q000378:metabolism*; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D059748:Proteolysis; D012307:Risk Factors
D024042:Collagen Type I; D020782:Matrix Metalloproteinases
C1M, MMP-mediated type I collagen degradation; CTX-I, Cathepsin K degraded products of C-terminal telopeptides of type I collagen; Clinical; ECM, Extracellular matrix; Extracellular matrix remodeling; MMP; MMP, Matrix metalloproteinase; Mortality; PERF I, Prospective Epidemiological Risk Factor study; PTM, Post-translational modification; Protease activity; Type I collagen