title: Tissue inhibitors of matrix metalloproteinases in serum are cardiac biomarkers in Emery-Dreifuss muscular dystrophy.
abstract: BACKGROUND
  Tissue inhibitors of matrix metalloproteinases (TIMPs) are known to be involved in cardiovascular diseases. Hitherto, they have not been examined in dilated cardiomyopathy in the course of Emery-Dreifuss muscular dystrophy (EDMD).
  
  
  OBJECTIVE
  To define TIMPs in serum because they might help in defining cardiac dysfunction at the early cardiological stages of this disease and detect preclinical stages of cardiomyopathy.
  
  
  METHODS
  Twenty-five EDMD patients connected with lamin A/C (AD-EDMD) or emerin (X-EDMD) deficiency and 20 healthy age-matched controls were examined. The serum levels of the tissue inhibitors TIMP-1, -2, -3 were quantified using the ELISA sandwich immunoassay procedure with appropriate antibodies.
  
  
  RESULTS
  Serum levels of TIMP-1 were normal in autosomal AD-EDMD and increased in the majority of X-linked EDMD. The level of TIMP-2 was decreased in 25%/21% of AD-EDMD/X-EDMD cases. TIMP-3 serum level was significantly reduced in all the examined patients. Receiver operating curves indicated that in terms of sensitivity and specificity characteristics the performance of TIMP-3 (less that of TIMP-2) makes them the best markers of cardiac involvement among the examined TIMPs.
  
  
  CONCLUSIONS
  Evidence shows that the levels of TIMP-3, and in some cases also TIMP-2, are decreased in EDMD. The decrease might be associated with an adverse effect on matrix metalloproteinases and remodelling of the myocardial matrix. The specific decrease of TIMP-3 indicates that this biomarker might help in early detection of cardiac involvement in EDMD. Up-regulation of TIMP-1 in the majority of patients with X-EDMD indicates increased myocardial extracellular matrix turnover, early onset of tissue remodelling, and may contribute to arrhythmia, frequently occurring in this form of the disease.
authors.affiliation: Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. neurmyol@imdik.pan.pl.
authors.forename: Irena Maria
authors.initials: IM
authors.lastname: Niebroj-Dobosz
authors.forename: Beata
authors.initials: B
authors.lastname: Sokołowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Madej-Pilarczyk
authors.forename: Michał
authors.initials: M
authors.lastname: Marchel
authors.forename: Irena
authors.initials: I
authors.lastname: Hausmanowa-Petrusewicz
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000097:blood* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000172:deficiency / Q000235:genetics; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000097:blood*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000097:blood* / Q000150:complications / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C494847:LMNA protein, human; D034904:Lamin Type A; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D009687:Nuclear Proteins; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; C088390:TIMP3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; C092710:emerin; D019716:Tissue Inhibitor of Metalloproteinase-2