Matrix Metalloproteinase Mediated Type I Collagen Degradation - An Independent Risk Factor for Mortality in Women

Katrine Dragsbæk Madsen, J. S. Neergaard, H. B. Hansen, I. Byrjalsen, P. Alexandersen, S. N. Kehlet, A.-C. Bay-Jensen, C. Christiansen, M. A. Karsdal

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Abstract

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.
Original languageEnglish
JournalEBioMedicine
Volume2
Issue number7
Pages (from-to)723-729
Number of pages7
DOIs
Publication statusPublished - 2015
Externally publishedYes

Bibliographical note

Published under a Under a Creative Commons license

Keywords

  • Extracellular matrix remodeling
  • Clinical
  • Type I collagen
  • Mortality
  • MMP
  • Protease activity

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