title: Matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, B⁺ tenascin-C and ED-A⁺ fibronectin in dilated cardiomyopathy: potential impact on disease progression and patients' prognosis.
abstract: BACKGROUND
  Dilated cardiomyopathy (DCM) is associated with heart failure and increased mortality and there is no reliable biomarker to estimate patients' prognosis. During cardiac remodeling, an extensive reorganization of the extracellular matrix occurs. The study was aimed to investigate matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1) and fetal tenascin-C (B(+) Tn-C) and fibronectin (ED-A(+) Fn) variants known to be involved in that process.
  
  
  RESULTS
  In 187 patients with DCM, levels of MMP-9, TIMP-1 and B(+) Tn-C in serum as well as B(+) Tn-C and ED-A(+) Fn in tissue were quantified and subjected to univariate analysis. For all serum markers, concentrations above a calculated threshold were associated with decreased survival (MMP-9: p = 0.008, TIMP-1: p = 0.001, B(+) Tn-C: p < 0.001) and a significantly higher risk to die or undergo transplantation. In tissue, a reexpression of B(+) Tn-C and ED-A(+) Fn could be shown. Protein deposition levels of ≥4.5% for B(+) Tn-C and ≥2.1% for ED-A(+) Fn were associated with a significantly decreased survival (p = 0.001 for B(+) Tn-C, p = 0.031 for ED-A(+) Fn) and an increased risk to die or undergo transplantation. In a multivariate analysis, TIMP-1 is the superior parameter to predict transplantation free survival (p = 0.027).
  
  
  CONCLUSIONS
  Serum levels of MMP-9, TIMP-1 and B(+) Tn-C and tissue levels of B(+) Tn-C and ED-A(+) Fn are promising markers for risk assessment. The reoccurrence of ED-A(+) Fn and the availability of a human antibody usable as a vehicle for targeted drug delivery might be the basis for novel therapeutic strategies.
authors.affiliation: Department of Internal Medicine I, University Hospital Jena, Erlanger Allee 101, 07740 Jena, Germany. Electronic address: Marcus.Franz@med.uni-jena.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Franz
authors.forename: Alexander
authors.initials: A
authors.lastname: Berndt
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.forename: Kerstin
authors.initials: K
authors.lastname: Galler
authors.forename: Katja
authors.initials: K
authors.lastname: Grün
authors.forename: Christiane
authors.initials: C
authors.lastname: Porrmann
authors.forename: Franziska
authors.initials: F
authors.lastname: Reinbothe
authors.forename: Gerhard
authors.initials: G
authors.lastname: Mall
authors.forename: Peter
authors.initials: P
authors.lastname: Schlattmann
authors.forename: André
authors.initials: A
authors.lastname: Renner
authors.forename: Hans Reiner
authors.initials: HR
authors.lastname: Figulla
authors.forename: Christian
authors.initials: C
authors.lastname: Jung
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Küthe
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000097:blood* / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012307:Risk Factors; D019063:Tenascin / Q000097:blood* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: D015415:Biomarkers; C067625:FN1 protein, human; D005353:Fibronectins; C560822:TIMP1 protein, human; D019063:Tenascin; D019715:Tissue Inhibitor of Metalloproteinase-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Dilated cardiomyopathy; Fibronectin; MMP-9; Prognosis; TIMP-1; Tenascin-C