title: Cardiac troponin in ischemic cardiomyocytes: intracellular decrease before onset of cell death.
abstract: OBJECTIVE
  Cardiac troponin I (cTnI) and T (cTnT) are the most important biomarkers in the diagnosis of acute myocardial infarction (AMI). Nevertheless, they can be elevated in the absence of AMI. It is unclear if such elevations represent irreversible cardiomyocyte-damage or leakage from viable cardiomyocytes. Our objective is to evaluate whether cTn is released from viable cardiomyocytes in response to ischemia and to identify differences in the release of cTn and its molecular forms.
  
  
  RESULTS
  HL-1 cardiomyocytes (mouse) were subjected to ischemia (modeled by anoxia with glucose deprivation). The total contents and molecular forms of cTn were determined in culture media and cell lysates. Cell viability was assessed from the release of lactate dehydrogenase (LDH). Before the release of LDH, the intracellular cTn content in ischemic cells decreased significantly compared to control (52% for cTnI; 23% for cTnT) and was not matched by a cTn increase in the medium. cTnI decreased more rapidly than cTnT, resulting in an intracellular cTnT/cTnI ratio of 25.5 after 24 h of ischemia. Western blots revealed changes in the relative amounts of fragmented cTnI and cTnT in ischemic cells.
  
  
  CONCLUSIONS
  HL-1 cardiomyocytes subjected to simulated ischemia released cTnI and cTnT only in combination with the release of LDH. We find no evidence of cTn release from viable cardiomyocytes, but did observe a significant decrease in cTn content, before the onset of cell death. Intracellular decrease of cTn in viable cardiomyocytes can have important consequences for the interpretation of cTn values in clinical practice.
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Streng
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Leo H J
authors.initials: LH
authors.lastname: Jacobs
authors.affiliation: Department of Molecular Genetics and Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Schwenk
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Eline P M
authors.initials: EP
authors.lastname: Cardinaels
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Steven J R
authors.initials: SJ
authors.lastname: Meex
authors.affiliation: Department of Molecular Genetics and Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Jan F C
authors.initials: JF
authors.lastname: Glatz
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Will K W H
authors.initials: WK
authors.lastname: Wodzig
authors.affiliation: Department of Clinical Chemistry, Maastricht University Medical Centre, Maastricht, The Netherlands. Electronic address: mp.van.dieijen.visser@mumc.nl.
authors.forename: Marja P
authors.initials: MP
authors.lastname: van Dieijen-Visser
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D007511:Ischemia / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000175:diagnosis*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D019210:Troponin I / Q000378:metabolism*; D020107:Troponin T / Q000378:metabolism*
chemical_list: D019210:Troponin I; D020107:Troponin T; D007770:L-Lactate Dehydrogenase
keywords: Cardiac ischemia; Cardiac troponin I; Cardiac troponin T; Cell death; HL-1 cardiomyocytes