title: Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker.
abstract: BACKGROUND
  Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical setting, we aimed to develop an assay that could reliably measure fragments of degraded titin in serum and potentially be used in the assessment of cardiac muscle damage.
  
  
  METHODS
  A competitive ELISA was developed to specifically measure levels of the titin sequence 12670' NVTVEARLIK 12679', derived by the degradation of titin by matrix metalloproteinase (MMP)-12. Serum samples from 90 individuals were divided into 3 equally sized groups. One group had been diagnosed with acute myocardial infarction (AMI) while the remaining two were asymptomatic individuals either with CT-scan signs of coronary calcium (CT-plusCa) or without coronary calcium (CT-noCa).
  
  
  RESULTS
  Mean geometric levels of the titin fragment in the CT-noCa group were 506.5 ng/ml (± 43.88). The CT-plusCa group showed 50.6% higher levels of the marker [763 ng/ml (± 90.14)] (P < 0.05). AMI patients showed 56.3% higher levels [792 ng/ml (± 149)] (P < 0.05).
  
  
  CONCLUSIONS
  The titin-12670 fragment is present in both individuals with undiagnosed and diagnosed CVD. The statistically significant increase in level of the marker in the AMI group is indicative that this neoepitope biomarker may be a useful serological marker in AMI.
authors: Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730, Herlev, Denmark. eva@nordicbioscience.com
authors: Efstathios
authors: E
authors: Vassiliadis
authors: Lars M
authors: LM
authors: Rasmussen
authors: Inger
authors: I
authors: Byrjalsen
authors: Dorthe Vang
authors: DV
authors: Larsen
authors: Rajiv
authors: R
authors: Chaturvedi
authors: Susanne
authors: S
authors: Hosbond
authors: Lotte
authors: L
authors: Saabye
authors: Axel C P
authors: AC
authors: Diederichsen
authors: Federica
authors: F
authors: Genovese
authors: Kevin L
authors: KL
authors: Duffin
authors: Qinlong
authors: Q
authors: Zheng
authors: Xiaoliang
authors: X
authors: Chen
authors: Diana J
authors: DJ
authors: Leeming
authors: Claus
authors: C
authors: Christiansen
authors: Morten A
authors: MA
authors: Karsdal
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D064211:Connectin; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D059748:Proteolysis; D012372:ROC Curve
chemical_list: D015415:Biomarkers; D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases; D053508:Matrix Metalloproteinase 12