Posttranslational modifications of cardiac troponin T: An overview

Objective The aim of this study was to determine the utility of oral fluids for assessment of coronary and cardiovascular (CV) health. Study Design Twenty-nine patients with preexisting CV disease underwent an invasive cardiac procedure (alcohol septal ablation or percutaneous coronary intervention) and provided unstimulated whole saliva (UWS), sublingual swabs (LS), gingival swabs (GS) and serum at 0, 8, 16, 24, and 48 hours. Concentrations of 13 relevant biomarkers were determined and correlated with levels in serum and the oral fluids. Results Concentrations of the majority of biomarkers were higher in UWS than in LS and GS. Coronary and CV disease biomarkers in UWS correlated better with serum than with LS and GS based on group status and measures of time effect. Seven biomarkers demonstrated time effect changes consistent with serum biomarkers, including C-reactive protein and troponin I. Conclusions Changes in serum biomarker profiles are reflected in oral fluids suggesting that oral fluid biomarkers could aid in the assessment of cardiac ischemia/necrosis.

/pdf/oral-fluids-that-detect-cardiovascular-disease-biomarkers-4xuap8vufr.pdf

Oral fluids that detect cardiovascular disease biomarkers.

Cardiac troponin T (cTnT), a protein essential for calcium-regulated, myofibrillar ATPase activity, is extremely sensitive to the action of a significant number of intra- and extracellular enzymes, the action of which causes post-translational modifications (PTMs) of amino acid structure and functioning cTnT. PTMs of cTnT may play important roles in the regulation of cardiac contractility. The vast majority of cTnT modifications involve the phosphorylation by a variety of Ser/Thr kinases, including PKC. At the same time, the activity of cTnT phosphorylation can change under physiological conditions and in some CVDs, including HF, AMI, and arrhythmias. Along with cTnT phosphorylation, cTnT fragmentation occurs, the activity of which can also change. This article discusses the mechanisms of cTnT phosphorylation and fragmentation, discusses the important role of these processes in the pathophysiology and laboratory diagnosis of some CVD, and notes promising directions for further research.

/pdf/phosphorylation-and-fragmentation-of-the-cardiac-troponin-t-39765dmlqv.pdf

Phosphorylation and Fragmentation of the Cardiac Troponin T: Mechanisms, Role in Pathophysiology and Laboratory Diagnosis

To the Editor:

The monoclonal antibody (MAb)1 8I-7 (International Point of Care Inc.) has been considered a sensitive tool for the detection of human cardiac troponin I (cTnI) for at least 15 years (1). It has been used in several cTnI assays and in different cTnI studies (1–5). According to the manufacturer's data, 8I-7 is specific to the epitope comprising amino acid residues 137–148 of the cTnI molecule.

In the March issue of Clinical Chemistry , Savukoski et al. (2) presented a study dedicated to evaluating the epitope specificity of autoantibodies to cTnI (cTnAAbs). In this study, commercial anti-cTnI MAbs specific to different epitopes were used as capture antibodies in sandwich immunoassays with an anti–troponin C MAb used as a tracer. The authors estimated the inhibition of signal after spiking in cTnAAb-positive and cTnAAb-negative (as a control) samples with a ternary troponin complex. The study showed that the anti-TnI MAbs specific to the region located between residues 65 and 158 …

Epitope Specificity of Anti–Cardiac Troponin I Monoclonal Antibody 8I-7

BACKGROUND: Cardiac troponin (cTn) is key in diagnosing myocardial infarction (MI). After MI, the clinically observed half-life of cTn has been reported to be 7 to 20 hours, but this estimate reflects the combined elimination and simultaneous release of cTn from cardiomyocytes. More precise timing of myocardial injuries necessitates separation of these 2 components. We used a novel method for determination of isolated cTn elimination kinetics in humans. METHODS: Patients with MI were included within 24 hours after revascularization and underwent plasmapheresis to obtain plasma with a high cTn concentration. After at least 3 weeks, patients returned for an autologous plasma retransfusion followed by blood sampling for 8 hours. cTn was measured with 5 different high-sensitivity cTn assays. RESULTS: Of 25 included patients, 20 participants (mean age, 64.5 years; SD, 8.2 years; 4 women [20%]) received a retransfusion after a median of 5.8 weeks (interquartile range, 5.0–6.9 weeks) after MI. After retransfusion of a median of 620 mL (range, 180–679 mL) autologous plasma, the concentration of cTn in participants’ blood increased 4 to 445 times above the upper reference level of the 5 high-sensitivity cTn assays. The median elimination half-life ranged from 134.1 minutes (95% CI, 117.8–168.0) for the Elecsys high-sensitivity cTnT assay to 239.7 minutes (95% CI, 153.7–295.1) for the Vitros high-sensitivity cTnI assay. The median clearance of cTnI ranged from 40.3 mL/min (95% CI, 32.0–44.9) to 52.7 mL/min (95% CI, 42.2–57.8). The clearance of cTnT was 77.0 mL/min (95% CI, 45.2–95.0). CONCLUSIONS: This novel method showed that the elimination half-life of cTnI and cTnT was 5 to 16 hours shorter than previously reported. This indicates a considerably longer duration of cardiomyocyte cTn release after MI than previously thought. Improved knowledge of timing of myocardial injury may call for changes in the management of MI and other disorders with myocardial injury. 

Half-Life and Clearance of Cardiac Troponin I and Troponin T in Humans

Introduction: Troponin has become the most important marker for diagnosing acute myocardial infarction, yet knowledge is scarce regarding appearance of specific degradation fragment

Cardiac Troponin I Degradation in Serum of Patients with Hypertrophic Obstructive Cardiomyopathy Undergoing Percutaneous Septal Ablation

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Cardiac Troponin I Degradation in Serum of Patients with Hypertrophic Obstructive Cardiomyopathy Undergoing Percutaneous Septal Ablation