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MMP‐9 Generated Collagen I C‐propeptides Alter Cardiac Fibroblast Function
Author(s) -
Castro Bras Lisandra E,
Dai Qiuxia,
Zamilpa Rogelio,
Fields Gregg B,
Weintraub Susan T,
Lindsey Merry L
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1059.3
Subject(s) - matrix metalloproteinase , protein precursor , chemistry , fibroblast , type i collagen , ventricular remodeling , myocardial infarction , extracellular matrix , medicine , metalloproteinase , collagen, type i, alpha 1 , ventricle , endocrinology , microbiology and biotechnology , biology , biochemistry , enzyme , in vitro
Heart failure is the result of adverse remodeling of the collagenous scar that replaces the damaged myocardium after myocardial infarction (MI). Post‐MI, specific matrix metalloproteinases (MMPs) increase and mediate left ventricle (LV) remodeling. Of the MMPs family members, MMP‐9 levels have been correlated with cardiovascular mortality in humans. Animal models show that MMP‐9 levels increase early post‐MI, and MMP‐9 deletion in mice attenuates remodeling. We found that C‐terminal propeptide (C‐propeptide) levels of á2(I) collagen were reduced in MMP‐9 null mice. Also, we have recently found a novel MMP‐9 recognition site that generates a C‐propeptide of 30 kDa. We used increasing doses of collagen fragments from the C‐terminus domain to stimulate cardiac fibroblasts and determine the mechanisms whereby C‐ propeptides regulate collagen function. We identified one fragment that strongly enhanced collagen I synthesis, suggesting a positive feedback loop between collagen processing and collagen synthesis. These results indicate that in addition to mediating ECM degradation, MMP‐9 may also regulate collagen I synthesis post‐MI.