Cardiac troponin T degradation in serum is catalysed by human thrombin

Streng, Alexander S.; Boer, Douwe de; Doorn, William P T M van; Kocken, Jordy M.M.; Bekers, Otto; Wodzig, Will K. W. H.

doi:10.1016/j.bbrc.2016.10.149

Cited by 24 publications

(22 citation statements)

References 19 publications

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“…1) In cells of the reticuloendothelial system (intracellular cleavage by specific proteases); 93,94 2) In serum (extracellular cleavage by proteolytic enzymes). It has now been proven that an enzyme of the hemostasis system (thrombin) causes specific cleavage of the troponin T molecule into two fragments; [95][96][97][98] 3) Renal (glomerular) filtration. [99][100][101] Glomerular filtration is considered to be the most discussed and perhaps the key mechanism of cardiac troponin elimination in terms of clinical significance.…”

Section: Cardiac Troponins In Chronic Renal Failure: Mechanisms Of Elevation and Diagnostic Valuementioning

confidence: 99%

The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis

Chauin¹

2021

VHRM

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The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI) (ischemic necrosis of cardiac myocytes). Any type of reversible or irreversible cardiomyocyte injury can result in elevated serum cTnT and cTnI levels. Researchers and practitioners involved in the diagnosis and treatment of cardiovascular disease, including AMI, should know the key causes and mechanisms of elevated serum cTnT and cTnI levels. This will allow to reduce or completely avoid diagnostic errors and help to choose the most correct tactics for further patient management. The purpose of this article is to discuss the main causes and mechanisms of increase in cardiac troponins concentrations in frequently occurring physiological (physical exertion, psycho-emotional stress) and pathological conditions (inflammatory heart disease, pulmonary embolism, chronic renal failure and sepsis (systemic inflammatory response)) not related to myocardial infarction.

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Section: Cardiac Troponins In Chronic Renal Failure: Mechanisms Of Elevation and Diagnostic Valuementioning

confidence: 99%

The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis

Chauin¹

2021

VHRM

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“…However, it is also important to understand that the concentration of cardiac troponin isoforms in the blood serum depends not only on the mechanisms of troponin release from cardiomyocytes but also on the mechanisms of their elimination from the bloodstream. The most well-known methods for removing many proteins, in particular troponins, include cleavage by specific proteases inside the cells of the reticuloendothelial system; extracellular cleavage by proteases, such as thrombin; and renal filtration [75][76][77][78][79][80].…”

Section: Causes and Mechanisms Of Elevated Cardiac Troponins In Chronic Kidney Diseasementioning

confidence: 99%

Elevation Mechanisms and Diagnostic Consideration of Cardiac Troponins under Conditions Not Associated with Myocardial Infarction. Part 1

Chaulin

2021

Life

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Although cardiac troponins are considered the most specific biomarkers for the diagnosis of acute myocardial infarction (AMI), their diagnostic consideration goes far beyond the detection of this dangerous disease. The mechanisms of cardiac troponin elevation are extremely numerous and not limited to ischemic necrosis of cardiac myocytes. Practitioners should be well aware of the underlying pathological and physiological conditions that can lead to elevated serum levels of cardiac troponins to avoid differential diagnostic errors, which will be greatly increased if clinicians rely on laboratory data alone. This article presents a classification of the main causes of an elevation in cardiac troponins and discusses in detail the mechanisms of such elevation and the diagnostic consideration of cardiac troponins in some conditions not associated with AMI, such as physical exertion, inflammatory heart diseases (myocarditis and endocarditis), pulmonary embolism (PE), renal failure, and systemic inflammation (sepsis).

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“…While it has been proposed that the initial release of troponin into the blood is from the cytosolic pool, followed by a sustained release over days due to the gradual breakdown of the myofibrils [40], some evidence suggests that some fraction of cTnT may be bound in equilibrium based on the cTnT:tropomyosin binding constant and readily released following myocardial insult [41]. Continuing with downstream degradation and excretion, reports by Streng et al have described the subsequent degradation of cTnT by thrombin in the bloodstream [42] and appearance in urine following acute myocardial infraction [43]. We have previously shown that oxidative carbonylation of cardiac myosin binding protein C (cMyBP-C) results in loss of association with actin, proteasomal degradation, and actin-binding related functional impairment.…”

Section: Plos Onementioning

confidence: 99%

Acute total body ionizing gamma radiation induces long-term adverse effects and immediate changes in cardiac protein oxidative carbonylation in the rat

et al. 2020

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Radiation-induced heart disease presents a significant challenge in the event of an accidental radiation exposure as well as to cancer patients who receive acute doses of irradiation as part of radiation therapy. We utilized the spontaneously hypertensive Wistar-Kyoto rat model, previously shown to demonstrate drug-induced cardiomyopathy, to evaluate the acute and long-term effects of sub-lethal total body gamma irradiation at two, four, and fiftytwo weeks. We further examined irreversible oxidative protein carbonylation in the heart immediately following irradiation in the normotensive Wistar-Kyoto rat. Both males and females sustained weight loss and anemic conditions compared to untreated controls over a one-year period as reflected by reduced body weight and low red blood cell count. Increased inflammation was detected by elevated IL-6 serum levels selectively in males at four weeks. Serum cardiac troponin T and I analyses revealed signs of cardiomyopathy at earlier timepoints, but high variability was observed, especially at one year. Echocardiography at two weeks following 5.0Gy treatment revealed a significant decrease in cardiac output in females and a significant decrease in both diastolic and systolic volumes in males. Following 10.0Gy irradiation in the normotensive Wistar-Kyoto rat, the heart tissue showed an increase in total protein oxidative carbonylation accompanied by DNA damage indicated by an increase in γ-H2AX. Using proteomic analyses, we identified several novel proteins which showed a marked difference in carbonylation including those of mitochondrial origin and most notably, cardiac troponin T, one of the key proteins involved in cardiomyocyte contractility. Overall, we present findings of acute oxidative protein damage, DNA damage, cardiac troponin T carbonylation, and long-term cardiomyopathy in the irradiated animals.

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Cardiac troponin T degradation in serum is catalysed by human thrombin

Cited by 24 publications

References 19 publications

The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis

The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis

Elevation Mechanisms and Diagnostic Consideration of Cardiac Troponins under Conditions Not Associated with Myocardial Infarction. Part 1

Acute total body ionizing gamma radiation induces long-term adverse effects and immediate changes in cardiac protein oxidative carbonylation in the rat

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