scholarly journals Molecular Heterogeneity Has a Major Impact on the Measurement of Circulating N-Terminal Fragments of A- and B-Type Natriuretic Peptides

2004 ◽  
Vol 50 (9) ◽  
pp. 1576-1588 ◽  
Author(s):  
Minna Ala-Kopsala ◽  
Jarkko Magga ◽  
Keijo Peuhkurinen ◽  
Jaana Leipälä ◽  
Heikki Ruskoaho ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Natriuretic Peptides ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Gel Filtration ◽  
Reversed Phase ◽  
Molecular Forms ◽  
Molecular Heterogeneity ◽  
Healthy Individuals

Abstract Background: The N-terminal fragments of A- and B-type natriuretic peptides (NT-proANP and NT-proBNP) are powerful markers of cardiac function. The current assays require refinement with regard to standardization with native calibrators and the ability to detect the actual circulating forms. Methods: The following peptides were prepared with recombinant methods: NT-proANP, NT-proBNP, proBNP1–108, and Tyr0-proBNP77–108. Fifteen peptides of 13–22 amino acids, spanning the sequences of NT-proANP and NT-proBNP, were prepared by solid-phase peptide synthesis. Two immunoassays for NT-proANP and four for NT-proBNP were set up, each with a different epitope specificity. The assays were applied for the measurement of NT-proANP and NT-proBNP in healthy individuals and in patients with acute myocardial infarction. The circulating molecular forms were analyzed by gel-filtration and reversed-phase HPLC. Results: According to the HPLC analyses, circulating NT-proANP consists mainly of the full-length peptide, with some degradation at both ends. In contrast, circulating NT-proBNP is very heterogeneous. Most immunoreactive NT-proBNP is significantly smaller in size than NT-proBNP1–76, with truncation at both termini. The smallest fragments can be detected by assays directed at the central part of NT-proBNP only; assays directed at the ends gave 30–40% lower values. Despite the difference, the various assays correlated reasonably well with each other (r2 = 0.77–0.85). In patients with acute myocardial infarction, NT-proANP and NT-proBNP concentrations were 1.8–2.3 and 4.2–4.5 times higher than in healthy individuals. The development of heart failure further increased the concentrations. Conclusions: Molecular heterogeneity of the circulating forms causes a serious risk of preanalytical errors in assays for NT-proBNP and, to a lesser extent, NT-proANP. The development of a sandwich assay for NT-proBNP would be especially challenging. The most robust and reliable assays use antibodies directed at the central portions of NT-proANP or NT-proBNP.

Diagnostic efficacy of a new enzyme immunoassay for creatine kinase MB isoenzyme.

1984 ◽  
Vol 30 (8) ◽  
pp. 1399-1401 ◽  
Author(s):  
J J Fenton ◽  
S Brunstetter ◽  
W C Gordon ◽  
D F Rippe ◽  
M L Bell
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Creatine Kinase ◽  
Enzyme Immunoassay ◽  
Solid Phase ◽  
Correct Diagnosis ◽  
Diagnostic Efficacy ◽  
Creatine Kinase Mb ◽  
Sandwich Type ◽  
Sensitivity Specificity

Abstract A new commercial enzyme immunoassay kit for quantification of creatine kinase-MB (CK-MB) isoenzyme was compared with its electrophoretic determination with respect to efficacy in diagnosis of acute myocardial infarction. Enzygnost CK-MB (Behring Diagnostics) is a solid-phase "sandwich"-type enzyme immunoassay with antibodies to the B-subunit coated on plastic tubes and peroxidase-conjugated antibodies to the M-subunit added after incubation with sample. This kit is designed to measure only CK-MB and not CK-MM, CK-BB, adenylate kinase, or atypical CK molecules. The linear-regression equation comparing the two methods was: Enzygnost = 0.98 . electrophoresis - 0.72, with a correlation coefficient of r = 0.967 (n = 143). For 51 patients admitted for diagnosis of possible acute myocardial infarction, the Enzygnost kit achieved 100% sensitivity, specificity, and efficiency in predicting the correct diagnosis. Corresponding values for the electrophoretic assay were: 95.5% sensitivity, 93.1% specificity, and 94.1% efficiency. We conclude that this kit method provides an excellent alternative to electrophoresis.

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 ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Troponin I ◽  
Troponin T ◽  
Gel Filtration ◽  
Free Form ◽  
Plasma Samples ◽  
Full Size ◽  
Troponin Complex ◽  
Almost All

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.

scholarly journals Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era

2004 ◽  
Vol 43 (5) ◽  
pp. 757-763 ◽  
Author(s):  
Jari M. Tapanainen ◽  
Kai S. Lindgren ◽  
Timo H. Mäkikallio ◽  
Olli Vuolteenaho ◽  
Juhani Leppäluoto ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Sudden Cardiac Death ◽  
Natriuretic Peptides ◽  
Cardiac Death ◽  
Beta Blocking

Plasma Natriuretic Peptides up to 2 Years After Acute Myocardial Infarction and Relation to Prognosis: An OPTIMAAL Substudy

2005 ◽  
Vol 11 (7) ◽  
pp. 492-497 ◽  
Author(s):  
Iain B. Squire ◽  
Stein Ørn ◽  
Leong L. Ng ◽  
Cord Manhenke ◽  
Lorraine Shipley ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Natriuretic Peptides

Vigorous response in plasma N-terminal pro-brain natriuretic peptide (NT-BNP) to acute myocardial infarction

2004 ◽  
Vol 106 (2) ◽  
pp. 135-139 ◽  
Author(s):  
Denzil GILL ◽  
Timothy SEIDLER ◽  
Richard W. TROUGHTON ◽  
Timothy G. YANDLE ◽  
Christopher M. FRAMPTON ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Troponin T ◽  
Plasma Concentrations ◽  
Creatine Kinase Mb ◽  
Multiple Blood ◽  
Multiple Samples

Acute myocardial infarction (MI) results in activation of neurohormonal systems and increased plasma concentrations of myocardial enzymes and structural proteins. We hypothesized that plasma levels of N-terminal pro-brain natriuretic peptide (NT-BNP) would respond more vigorously after MI than those of other natriuretic peptides. We also sought to compare this response with that of the established myocardial injury markers troponin T (TnT), myoglobin and creatine kinase MB (CK-MB). We obtained multiple blood samples for measurement of atrial natriuretic peptide (ANP), N-terminal pro-ANP, brain natriuretic peptide (BNP) and NT-BNP along with CK-MB, TnT and myoglobin in 24 patients presenting to the Coronary Care Unit within 6 h of onset of MI. Multiple samples were obtained in the first 24 h, then at 72 h, 1 week, 6 weeks and 12 weeks. NT-BNP increased rapidly to peak at 24 h and exhibited greater (P<0.001) absolute increments from baseline compared with BNP and ANP, whereas NT-ANP did not change from baseline. Proportional increments in NT-BNP were also greater than those for the other natriuretic peptides (P<0.05). Natriuretic peptide levels reached their peak around 24 h, later than peak TnT, CK-MB and myoglobin (peak between 1–10 h), and NT-BNP and ANP remained elevated on average for 12 weeks. Our present results, with detailed sampling of a cohort of acute MI patients, demonstrate greater absolute and proportional increments in NT-BNP than ANP or BNP with sustained elevation of these peptides at 12 weeks.

scholarly journals Natriuretic Peptides as an Adjunctive Treatment for Acute Myocardial Infarction

2014 ◽  
Vol 55 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Ting Lyu ◽  
Yichao Zhao ◽  
Tuo Zhang ◽  
Wen Zhou ◽  
Fan Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Natriuretic Peptides ◽  
Adjunctive Treatment

scholarly journals The alteration of circulating exosomal mRNAs in acute myocardial infarction is associated with inflammation response mediated by neutrophils

2020 ◽  
Author(s):  
Guo-dong HE ◽  
Yu-qing HUANG ◽  
Lin LIU ◽  
Jia-yi HUANG ◽  
Kenneth Lo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Network Analysis ◽  
Immune Cell ◽  
Stable Coronary Artery Disease ◽  
Characteristic Curve ◽  
Diagnostic Efficiency ◽  
Messenger Rnas ◽  
Healthy Individuals ◽  
Clinical Value

Abstract Background Although many cardiovascular disease studies have focused on the characteristics of microRNAs in circulating exosomes, the profile and the potential clinical diagnostic value of plasma exosomal long RNAs (exoLRs) in acute myocardial infarction (AMI) is still unknown.Methods In this study, exosomes isolation and RNA sequencing were applied to achieve the circulating exoLRs profile of 10 AMI patients, 8 stable coronary artery disease (CAD) patients, and 10 healthy individuals. Bioinformatics approaches were used to investigate the features and potential clinical value of exoLRs.Results Each sample from 2 mL of plasma could reliably achieve more than 8000 exosomal messenger RNAs (mRNAs) making up a majority of the total exoLRs. Immune cell types analyzed by CIBERSORT showed that neutrophils and monocytes were significantly enriched in the AMI group compared to healthy individuals and the CAD group which were consistent with the clinical baseline characteristics. Similarly, the biological processes enrichment analyses of different exosomal mRNAs and co-expression network analysis both indicated that neutrophils activation associated processes were also significantly enriched in the AMI group. We further identified two exosomal mRNA ALPL and CXCR2 which might be served as potential biomarkers with high diagnostic efficiency through co-expression network analysis and receiver operating characteristic curve (ROC).Conclusions In summary, our study explored the alteration of exoLRs in the AMI patients which might associate with the acute inflammatory response mediated by neutrophils. We found that exosomal mRNAs ALPL and CXCR2 might be potentially useful for AMI diagnosis.

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