title: Low MMP-8/TIMP-1 reflects left ventricle impairment in takotsubo cardiomyopathy and high TIMP-1 may help to differentiate it from acute coronary syndrome.
abstract: BACKGROUND
  Matrix metalloproteinase 8 (MMP-8) is the most potent type-I collagen protease. Such collagen mainly constitutes the transient fibrosis in takotsubo cardiomyopathy (TTC) endomyocardial biopsies. High MMP-8 and tissue-inhibitor of matrix metalloproteinase-1 (TIMP-1) levels are implicated in acute coronary syndrome (ACS). We compared MMP-8 and TIMP-1 levels in consecutive TTC and ACS patients, and their association to TTC severity.
  
  
  RESULTS
  In 45 acute serum samples of TTC, 2072 ACS and 1000 controls, TIMP-1 differed between ACS 146.7ng/mL (115.0-186.3) (median (interquartile range)), TTC 115.7 (94.3-137.7) and controls 80.9 (73.2-90.4), (p<0.0001). MMP-8 levels were similar between ACS and TTC. In receiver-operating characteristics analysis, TIMP-1 differentiated TTC from ACS with an area under the curve (AUC) of 0.679 (p<0.0001) surpassing troponin T (TnT) at 0.522 (p = 0.66). Compared to other differing factors (age, sex, smoking), TIMP-1 improved diagnostic specificity and sensitivity from AUC of 0.821 to 0.844 (p = 0.007). The MMP8/TIMP-1 molar ratio differentiated normal ejection fraction (EF) at 0.27 (0.13-0.51) from decreased EF<50% at 0.08 (0.05-0.20), (p = 0.04) in TTC, but not in ACS.
  
  
  CONCLUSIONS
  Even with other differing factors considered, TIMP-1 differentiated TTC from ACS better than TnT. In TTC, the low MMP-8/TIMP-1 molar ratio may reflect decreased proteolysis and increased transient fibrosis, perhaps in part explaining the left-ventricle impairment.
authors.affiliation: Heart and Lung Center, Helsinki University Hospital and Helsinki University, Helsinki, Finland.
authors.forename: Olavi
authors.initials: O
authors.lastname: Parkkonen
authors.affiliation: Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mikko T
authors.initials: MT
authors.lastname: Nieminen
authors.affiliation: Heart and Lung Center, Helsinki University Hospital and Helsinki University, Helsinki, Finland.
authors.forename: Paula
authors.initials: P
authors.lastname: Vesterinen
authors.affiliation: Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Tervahartiala
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Jousilahti
authors.affiliation: Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.affiliation: Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Pirkko J
authors.initials: PJ
authors.lastname: Pussinen
authors.affiliation: Heart and Lung Center, Helsinki University Hospital and Helsinki University, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Sinisalo
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood*; D009200:Myocardial Contraction; D054549:Takotsubo Cardiomyopathy / Q000097:blood* / Q000175:diagnosis* / Q000201:enzymology / Q000503:physiopathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D018487:Ventricular Dysfunction, Left
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020784:Matrix Metalloproteinase 8