Cardiac troponin in ischemic cardiomyocytes: intracellular decrease before onset of cell death.

Abstract

AIM:

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.

METHODS AND 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: Alexander S Streng, Leo H J Jacobs, Robert W Schwenk, Eline P M Cardinaels, Steven J R Meex, Jan F C Glatz, Will K W H Wodzig, Marja P van Dieijen-Visser
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 96 Issue 3 Pg. 339-45 (Jun 2014) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 24607416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Troponin I
• Troponin T
• L-Lactate Dehydrogenase

Topics

• Animals
• Cell Death (physiology)
• Cell Hypoxia
• Cells, Cultured
• Ischemia (pathology)
• L-Lactate Dehydrogenase (metabolism)
• Mice
• Myocardial Infarction (diagnosis)
• Myocytes, Cardiac (metabolism, pathology)
• Troponin I (metabolism)
• Troponin T (metabolism)