Time-Dependent Degradation Pattern of Cardiac Troponin T Following Myocardial Infarction

BACKGROUNDCardiac troponin T (cTnT) is widely used for the diagnosis of acute myocardial infarction (AMI). However, it is still unclear whether degraded cTnT forms circulate in the patient's blood. We therefore aimed to elucidate which cTnT forms are detected by the clinical assay.METHODSSeparation of cTnT forms by gel filtration chromatography (GFC) was performed in sera from 13 AMI patients to examine cTnT degradation. The GFC eluates were subjected to Western blot analysis with the original antibodies from the Roche immunoassay used to mimic the clinical cTnT assay. To investigate the degradation pattern with time, standardized serum samples of 18 AMI patients collected 0–72 h after admission were analyzed by Western blot analysis.RESULTSGFC analysis of AMI patients' sera revealed 2 cTnT peaks with retention volumes of 5 and 21 mL. Western blot analysis identified these peaks as cTnT fragments of 29 and 14–18 kDa, respectively. Furthermore, the performance of direct Western blots on standardized serum samples demonstrated a time-dependent degradation pattern of cTnT, with fragments ranging between 14 and 40 kDa. Intact cTnT (40 kDa) was present in only 3 patients within the first 8 h after hospital admission.CONCLUSIONSThese results demonstrate that the Roche cTnT immunoassay detects intact as well as degraded cTnT forms in AMI patients' sera during the period of diagnostic testing. Moreover, following AMI, cTnT is degraded in a time-dependent pattern.

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Cardiac troponin T alterations in myocardium and serum of rats after stressful, prolonged intense exercise

Journal of Applied Physiology ◽

10.1152/jappl.2000.88.5.1749 ◽

2000 ◽

Vol 88 (5) ◽

pp. 1749-1755 ◽

Cited By ~ 87

Author(s):

Yingjie Chen ◽

Robert C. Serfass ◽

Shannon M. Mackey-Bojack ◽

Karen L. Kelly ◽

Jack L. Titus ◽

...

Keyword(s):

Left Ventricle ◽

Western Blot ◽

Blot Analysis ◽

Cardiac Troponin ◽

Western Blot Analysis ◽

Troponin T ◽

Male Rats ◽

Cardiac Troponin T ◽

Exercise Induced ◽

Myocyte Damage

The goal of this study was to determine whether the stress of forced exercise would result in injury to the myocardium. Male rats with 8% of body weight attached to the tail were forced to swim 3.5 h (3.5S), forced to swim 5 h (5S), or pretrained for 8 days and then forced to swim 5 h (T5S). Rats were killed immediately after they swam (0 h PS) and at 3 h (3 h PS), 24 h (24 h PS), and 48 h after they swam (48 h PS). Tissue homogenates of the left ventricle were analyzed by Western blot analysis for cardiac troponin T (cTnT). Serum cTnT was quantified by immunoassay. Results indicated that, in the 3.5S, 5S, and T5S groups, serum cTnT was significantly ( P < 0.01) increased at 0 and 3 h PS. The 5S group demonstrated a greater increase in serum cTnT than the 3.5S group ( P < 0.01) and the T5S group ( P < 0.01) at 0 h PS. Western blot analysis indicated significant decreases ( P < 0.01) in myocardial cTnT in the 5S group only at 0 h PS ( P < 0.01) and 3 h PS ( P < 0.05). Histological evidence of localized myocyte damage demonstrated by interstitial inflammatory infiltrates consisting of neutrophils, lymphocytes, and histiocytes, as well as vesicular nuclei-enlarged chromatin patterns, was observed in left ventricle specimens from the 5S group at 24 and 48 h PS. Our findings demonstrate that stressful, forced exercise induces alterations in myocardial cTnT and that training before exercise attenuates the exercise-induced heart damage.

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Time-Dependent Degradation Pattern of Cardiac Troponin T in Cases of Death by Burn

West Indian Medical Journal ◽

10.7727/wimj.2014.232 ◽

2015 ◽

Cited By ~ 2

Author(s):

S Kumar ◽

W Ali ◽

US Singh ◽

AK Verma ◽

S Bhattacharya ◽

...

Keyword(s):

Cardiac Troponin ◽

Troponin T ◽

Time Dependent ◽

Cardiac Troponin T ◽

Degradation Pattern

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P4503A multi-site coronary vein sampling study on cardiac troponin T degradation in non-ST-elevation myocardial infarction

European Heart Journal ◽

10.1093/eurheartj/ehz745.0896 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

G E Cramer ◽

S A J Damen ◽

W H M Vroemen ◽

S T P Mezger ◽

H Suryapranata ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Troponin ◽

Troponin T ◽

Cardiac Troponin T ◽

Peripheral Artery ◽

Serum Samples ◽

Coronary Vein ◽

C Complex ◽

Over Time

Abstract Background High-sensitivity cardiac troponin (hs-cTn) assays have reduced specificity for myocardial infarction (MI). In conditions other than MI, cardiac troponin T (cTnT) elevations have been attributed to small cTnT fragments. In search of improved cTnT assay specificity for MI, determination of the in-vivo molecular appearance of cTnT during MI is pivotal. Purpose To determine cTnT composition close to its site of release and during the course of MI by multi-site coronary venous system (CVS) and peripheral sampling. Methods Lithium-heparinized (LH) plasma and serum samples were obtained from multiple CVS locations in NSTEMI patients. Additionally, samples were drawn from a peripheral artery and vein followed by collections at 6- and 12 hours post-catheterization. cTnT concentrations were measured using the hs-cTnT immunoassay (Roche). The molecular cTnT composition was determined by gel filtration chromatography and Western blotting in an early and late presenting patient. Results CVS hs-cTnT concentrations were 28% higher than in the peripheral artery sample (n=71, p<0.001). In contrast to LH plasma, serum caused pre-analytical cTn T-I-C complex disintegration and cTnT degradation. CVS samples demonstrated presence of cTn T-I-C complex, free intact cTnT, and 29 kDa and 15–18 kDa cTnT fragments in higher absolute concentrations than measured peripherally. While the proportion of cTn T-I-C complex decreased and disappeared over time, 15–18 kDa cTnT fragments increased. Moreover, cTn T-I-C complex was more prominent in the early versus the late presenting patient. Central illustration Conclusions In NSTEMI, cTnT is released as a combination of cTn T-I-C complex, free intact cTnT and multiple cTnT fragments. Over time, the composition of observed cTnT forms changes due to in-vivo degradation. These findings serve as a stepping stone to improve diagnostic accuracy of the hs-cTnT assay for MI.

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