scholarly journals Full-Size and Partially Truncated Cardiac Troponin Complexes in the Blood of Patients with Acute Myocardial Infarction

2019 ◽  
Vol 65 (7) ◽  
pp. 882-892 ◽  
Author(s):  
Alexandra V Vylegzhanina ◽  
Alexander E Kogan ◽  
Ivan A Katrukha ◽  
Ekaterina V Koshkina ◽  
Anastasia V Bereznikova ◽  
...  

AbstractBACKGROUNDThe measurement of cardiac isoforms of troponin I (cTnI) and troponin T (cTnT) is widely used for the diagnosis of acute myocardial infarction (AMI). However, there are conflicting data regarding what forms of cTnI and cTnT are present in the blood of AMI patients. We investigated cTnI and cTnT as components of troponin complexes in the blood of AMI patients.METHODSGel filtration techniques, sandwich fluoroimmunoassays, and Western blotting were used.RESULTSPlasma samples from patients with AMI contained the following troponin complexes: (a) a cTnI-cTnT-TnC complex (ITC) composed of full-size cTnT of 37 kDa or its 29-kDa fragment and full-size cTnI of 29 kDa or its 27-kDa fragments; (b) ITC with lower molecular weight (LMW-ITC) in which cTnT was truncated to the 14-kDa C-terminal fragments; and (c) a binary cTnI-cTnC complex composed of truncated cTnI of approximately 14 kDa. During the progression of the disease, the amount of ITC in AMI samples decreased, whereas the amounts of LMW-ITC and short 16- to 20-kDa cTnT central fragments increased. Almost all full-size cTnT and a 29-kDa cTnT fragment in AMI plasma samples were the components of ITC. No free full-size cTnT was found in AMI plasma samples. Only 16- to 27-kDa central fragments of cTnT were present in a free form in patient blood.CONCLUSIONSA ternary troponin complex exists in 2 forms in the blood of patients with AMI: full-size ITC and LMW-ITC. The binary cTnI-cTnC complex and free cTnT fragments are also present in patient blood.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Stanley Chia ◽  
O. Christopher Raffel ◽  
Faisal Merchant ◽  
Frans J Wackers ◽  
Fred Senatore ◽  
...  

Background: Assessment of cardiac biomarker release has been traditionally used to estimate the size of myocardial damage after acute myocardial infarction (AMI). However, the significance of cardiac biomarkers in the setting of primary percutaneous coronary intervention (PCI) has not been systematically studied in a large patient cohort. We evaluated the usefulness of serial and single time-point measures of various cardiac biomarkers (creatine kinase (CK), CK-MB, troponin T and I) in predicting infarct size and left ventricular ejection fraction (LVEF) after primary PCI. Methods: EVOLVE (Evaluation of MCC-135 for Left Ventricular Salvage in AMI) was a randomized double-blind, placebo-controlled trial comparing the efficacy of intracellular calcium modulator as an adjunct to primary PCI in patients with first large AMI. Levels of cardiac biomarkers (CK, CK-MB mass, troponin T and I) were determined in 375 patients at baseline before PCI and 2, 4, 12, 24, 48 and 72 hours thereafter. Single photon emission computed tomography imaging was performed to measure infarct size and LVEF on day 5. Results: Area under curve and peak concentrations of all cardiac markers: CK, CK-MB mass, troponin T and troponin I were significantly correlated with myocardial infarct size and LVEF determined on day 5 (Spearman correlation, all P< 0.001; Table ). Troponin I, however provided the best predictor and a single measure at 72 hr was a strong indicator of both infarct size and LVEF. Using receiver operator characteristics curve, troponin I cutoff value of >55 pg/mL at 72 hr has 90% sensitivity and 70% specificity for detection of large infarct size≥10% ( c =0.88; P< 0.001). Conclusions: Plasma levels of CK, CK-MB, troponin T and troponin I remain useful predictors of infarct size and cardiac function in the era of primary PCI for AMI. A single measurement of circulating troponin I at 72 hours can provide an effective and convenient indicator of infarct size and LVEF in clinical practice. Correlation of cardiac biomarkers with Day 5 SPECT determined infarct size and LVEF


1998 ◽  
Vol 44 (6) ◽  
pp. 1198-1208 ◽  
Author(s):  
Alan H B Wu ◽  
Yue-Jin Feng ◽  
Robert Moore ◽  
Fred S Apple ◽  
Paul H McPherson ◽  
...  

Abstract We examined the release of cardiac troponin T (cTnT) and I (cTnI) into the blood of patients after acute myocardial infarction (AMI). Three postAMI serum samples were applied in separate analytical runs onto a calibrated gel filtration column (Sephacryl S-200), and the proteins were separated by molecular weight. Using commercial cTnT and cTnI assays measured on collected fractions, we found that troponin was released into blood as a ternary complex of cTnT-I-C, a binary complex of cTnI-C, and free cTnT, with no free cTnI within the limits of the analytical methodologies. The serum samples were also examined after incubation with EDTA and heparin. EDTA broke up troponin complexes into individual subunits, whereas heparin had no effect on the assays tested. We added free cTnC subunits to 24 AMI serum samples and found no marked increase in the total cTnI concentrations, using an immunoassay that gave higher values for the cTnI-C complex than free cTnI. To characterize the cross-reactivity of cTnT and cTnI assays, purified troponin standards in nine different forms were prepared, added to serum and plasma pools, and tested in nine quantitative commercial and pre-market assays for cTnI and one approved assay for cTnT. All nine cTnI assays recognized each of the troponin I forms (complexed and free). In five of these assays, the relative responses for cTnI were nearly equimolar. For the remainder, the response was substantially greater for complexed cTnI than for free cTnI. Moreover, there was a substantial difference in the absolute concentration of results between cTnI assays. The commercial cTnT assay recognized binary and ternary complexes of troponin on a near equimolar basis. We conclude that all assays are useful for detection of cardiac injury. However, there are differences in absolute cTnI results due to a lack of mass standardization and heterogeneity in the cross-reactivities of antibodies to various troponin I forms.


1997 ◽  
Vol 43 (8) ◽  
pp. 1379-1385 ◽  
Author(s):  
Aleksei G Katrukha ◽  
Anastasia V Bereznikova ◽  
Tatiana V Esakova ◽  
Kim Pettersson ◽  
Timo Lövgren ◽  
...  

Abstract Fourteen monoclonal antibodies (mAbs) against human cardiac troponin I (cTnI) were generated by commonly used experimental techniques. All these antibodies, as well as antibody 414 (HyTest), were specific for human cTnI. Fifteen antibodies thus obtained were tested in a sandwich cTnI immunofluorescence assay (altogether 196 combinations). Ten pairs giving the highest sensitivity were selected for further investigation. The effect of TnI–TnC complex formation on antibody interaction with antigen was analyzed. The formation of TnI–TnC complex results in a significant decrease of the interaction of mAbs with TnI for seven of 10 analyzed pairs of antibodies. Using two pairs of cTnI-specific mAbs, one that recognized only free cTnI but not cTnI complexed with cTnC, and another that could be used for measurement of total cTnI (free cTnI and cTnI in complex with cTnC), we demonstrated that the main part of cTnI in serum collected from acute myocardial infarction patients is presented in the complex form. We concluded that effective and reliable immunological detection of TnI is possible only when antibodies used for assay development recognize both free TnI and TnI complexed with other troponin components.


2016 ◽  
Vol 38 (3) ◽  
pp. 1015-1029 ◽  
Author(s):  
Ke-Jing Wang ◽  
Xin Zhao ◽  
Yu-Zhou Liu ◽  
Qiu-Tang Zeng ◽  
Xiao-Bo Mao ◽  
...  

Background/Aims: Recent studies have shown that circulating microRNAs (miRNAs) are emerging as promising biomarkers for cardiovascular diseases. This study aimed to determine whether miR-19b-3p, miR-134-5p and miR-186-5p can be used as novel indicators for acute myocardial infarction (AMI). Methods: To investigate the kinetic expression of the three selected miRNAs, we enrolled 18 patients with AMI and 20 matched controls. Plasma samples were collected from each participant, and total RNA was extracted. Quantitative real-time PCR and ELISA assays were used to investigate the expression of circulating miRNAs and cardiac troponin I (cTnI), respectively. Plasma samples from another age- and gender-matched cohort were collected to investigate the impact of medications for AMI on the expression of the selected miRNAs. Results: Levels of plasma miR-19b-3p, miR-134-5p and miR-186-5p were significantly increased in early stage of AMI. Plasma miR-19b-3p and miR-134-5p levels reached peak expression immediately after admission (T0), whereas miR-186-5p achieved peak expression at 4 h after T0. All of these times were earlier than the peak for cTnI (8 h after T0). In addition, all three miRNAs were positively correlated with cTnI. Receiver Operating Characteristic (ROC) analysis indicated that each single miRNA showed considerable diagnostic efficiency for predicting AMI. Furthermore, combining all three miRNAs in a panel increased the efficiency of distinguishing between patients with AMI and controls. Moreover, we found that heparin and medications for AMI did not impact the expression of these circulating miRNAs. Conclusion: Circulating miR-19b-3p, miR-134-5p and miR-186-5p could be considered promising novel diagnostic biomarkers for the early phase of AMI.


Author(s):  
Kamila Solecki ◽  
Anne Marie Dupuy ◽  
Nils Kuster ◽  
Florence Leclercq ◽  
Richard Gervasoni ◽  
...  

AbstractCardiac biomarkers are the cornerstone of the biological definition of acute myocardial infarction (AMI). The key role of troponins in diagnosis of AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine kinase (CK) after AMI are correlated to the prognosis. New technical assessment like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its unclear kinetic following the peak. This study aims to compare kinetics of cTnI and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous coronary intervention (PCI).We prospectively studied 62 patients with anterior AMI successfully reperfused with primary angioplasty. We evaluated two consecutive groups: the first one regularly assessed by both CK and cTnI methods and the second group by CK and hs-cTnT. Modeling of kinetics was realized using mixed effects with cubic splines.Kinetics of markers showed a peak at 7.9 h for CK, at 10.9 h (6.9–12.75) for cTnI and at 12 h for hs-cTnT. This peak was followed by a nearly log linear decrease for cTnI and CK by contrast to hs-cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h. There was no significant difference between the decrease of cTnI and CK (p=0.63). CK fell by 79.5% (76.1–99.9) vs. cTnI by 86.8% (76.6–92.7). In the hs-cTnT group there was a significant difference in the decrease by 26.5% (9–42.9) when compared with CK that fell by 79.5% (64.3–90.7).Kinetic of hs-cTnT and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be investigated.


2011 ◽  
Vol 152 (38) ◽  
pp. 1528-1534 ◽  
Author(s):  
Eszter Szánthó ◽  
Zoltán Szabó ◽  
József Varga ◽  
György Paragh ◽  
Anna V. Oláh

Troponin is the first choice in the diagnosis of acute myocardial infarction. Correct interpretation is challenging, because high sensitive troponin tests used today detect even the smallest cardiac damage. Methods: High sensitive troponin T (Roche) and troponin I (Mitsubishi Pathfast) and creatine-kinase activity were measured in 20 patients, each having two samples with the time lapse 3–9 hours. Results: In the group without acute myocardial infarction (n = 10) no significant increase in creatine-kinase and creatine-kinase-MB levels were seen, and the mild raise of troponins was due to other cardiovascular problems (atrial fibrillation, paroxysmal supraventricular tachycardia). With acute myocardial infarction (n = 10) a dramatic increase of troponin levels was found in the second samples, and also an increase of creatine-kinase and creatine-kinase-MB activity. According to Fischer-probe a twofold or higher increase of troponin implies 19-times higher risk of acute myocardial infarction in the case of troponin T and 8-times odds ratio at troponin I. Conclusions: The patient’s accompanying diseases should always be considered. If the troponin level is elevated, the measurement should be repeated within 3–6 hours. When troponin shows at least a twofold increase and the patient has chest pain or positive ECG, AMI is likely, and the patient needs special medical care. Although the first troponin level might be elevated if accompanying diseases cause chronic cardiac damage, it can be differentiated by a second troponin measurement. Orv. Hetil., 2011, 152, 1528–1534.


2017 ◽  
Vol 63 (1) ◽  
pp. 343-350 ◽  
Author(s):  
Alexandra V Vylegzhanina ◽  
Alexander E Kogan ◽  
Ivan A Katrukha ◽  
Olga V Antipova ◽  
Andrey N Kara ◽  
...  

Abstract BACKGROUND Autoantibodies to cardiac troponins (TnAAbs) could negatively affect cardiac troponin I (cTnI) measurements by TnAAbs-sensitive immunoassays. We investigated the epitope specificity of TnAAbs and its influence on cTnI immunodetection in patients with acute myocardial infarction (AMI). METHODS The specificity of TnAAbs was studied in immunoassays and gel-filtration experiments. The influence of TnAAbs on endogenous troponin measurements was studied in 35 plasma samples from 15 patients with AMI. RESULTS The inhibitory effect of TnAAbs on the cTnI immunodetection was observed only for the ternary cardiac troponin complex (I–T–C) and not for the binary cardiac troponin complex (I–C) or free cTnI. In the same TnAAbs-containing samples, the immunodetection of cardiac troponin T (cTnT) added in the form of I–T–C (but not free cTnT) was also inhibited in the assays that used monoclonal antibodies (mAbs) specific to the 223–242 epitope. The negative effects of TnAAbs on the measurements of endogenous cTnI in AMI samples were less than on the measurements of isolated I–T–C and decreased with time after the onset of symptoms. Early AMI blood samples might contain a mixture of the I–T–C and I–C complexes with the ratio gradually changing with the progression of the disease in favor of I–C. CONCLUSIONS The investigated TnAAbs are specific to the structural epitopes formed by cTnI and cTnT molecules in the I–T–C complex. AMI blood samples contain a mixture of I–C and I–T–C complexes. The concentrations of total cTnI at the early stage of AMI could be underestimated in approximately 5%–10% of patients if measured by TnAAbs-sensitive immunoassays.


2015 ◽  
Vol 156 (24) ◽  
pp. 964-971
Author(s):  
Ferenc Kovács ◽  
Ibolya Kocsis ◽  
Marina Varga ◽  
Enikő Sárváry ◽  
György Bicsák

Introduction: Cardiac biomarkers have a prominent role in the diagnosis of acute myocardial infarction. Aim: The aim of the authors was to study the diagnostic effectiveness of automated measurement of cardiac biomarkers. Method: Myeloperoxidase, high-sensitivity C-reactive protein, myoglobin, heart-type fatty acid binding protein, creatine kinase, creatine kinase MB, high-sensitivity troponin I and T were measured. Results: The high-sensitivity troponin I was the most effective (area under curve: 0.86; 95% confidence interval: 0.77–0.95; p<0.001) for the diagnosis of acute myocardial infarction. Considering a critical value of 0.35 ng/mL, its sensitivity and specificity were 81%, and 74%, respectively. Combined evaluation of the high-sensitivity troponin T and I, chest pain, and the electrocardiogram gave the best results for separation of acute myocardial infarction from other diseases (correct classification in 62.5% and 98.9% of patients, respectively). Conclusions: Until a more sensitive and specific cardiac biomarker becomes available, the best method for the diagnosis of acute myocardial infarction is to evaluate electrocardiogram and biomarker concentration and to repeat them after 3–6 hours. Orv. Hetil., 2015, 156(24), 964–971.


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