Biochemistry of B-type natriuretic peptide – where are we now?
-
Johannes Mair
Abstract
Background: The discovery of the cardiac endocrine function more than 25 years ago was a breakthrough for the implementation of a routine laboratory marker of heart failure. The heart secretes two different natriuretic peptides with similar biological effects. B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) emerged as the superior diagnostic markers compared to circulating A-type natriuretic peptide (ANP) and proANP derived peptide forms. However, the biochemistry with the processing and metabolism of proBNP, NT-proBNP and BNP with their impact on BNP quantification are still incompletely understood.
Methods: Published data and own results were used.
Results: This review shows that the present understanding of the biochemistry of BNP and its circulating forms is far from complete. The regulation of BNP secretion occurs mainly at the level of gene transcription with only minor stores of proBNP and processed BNP 1–32 within cardiomyocytes. proBNP is believed to be split into BNP 1–32 and NT-proBNP 1–76 mainly upon secretion, although limited amounts of processed BNP have also been described in the secretory granules of atrial cardiomyocytes. proBNP can be also detected in the circulation and exists as a monomer. There is no evidence for relevant processing of proBNP into BNP 1–32 and NT-proBNP in the circulation. Only small amounts of the intact hormone BNP 1–32 appear to circulate in plasma, there are no known BNP binding proteins. The major circulating BNP forms appear to be split products of BNP 1–32, but are still not sufficiently characterized. Dipeptidyl-peptidase IV degrades BNP 1–32 to BNP 3–32 at its N-terminal end. NT-proBNP appears to be rapidly truncated at both ends as well. proBNP and NT-proBNP are glycosylated to a variable degree. BNP and NT-proBNP are extracted by the kidneys to a comparable extent. In contrast to BNP, the biological half-life of NT-proBNP in humans is still not known. The current commercial BNP assays do not significantly cross-react with NT-proBNP and vice versa. However, BNP as well as NT-proBNP assays cross-react with proBNP to a varying extent.
Conclusions: The better characterization of circulating proBNP, BNP, and NT-proBNP forms is necessary to define the relevant standard for assay standardization. Until then, assays should be designed to detect the total amount of the circulating analyte to achieve optimal sensitivity. The identification of possible disease effects on proBNP, BNP, and NT-proBNP metabolism could pave the way for the development of more disease specific assays in the clinical setting.
Clin Chem Lab Med 2008;46:1507–14.
©2008 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Editorial
- Biochemical markers in clinical cardiology: perspectives from present to future. 1st IFCC-Ortho Clinical Diagnostics Conference on Clinical Diagnosis and the Clinical Laboratory
- Highlight: Cardiovascular Biomarkers
- Reviews
- The clinical impact of the universal diagnosis of myocardial infarction
- Troponin revisited 2008: assay performance
- Standardization of troponin I measurements: an update
- Biochemistry of B-type natriuretic peptide – where are we now?
- Clinical relevance of non-cardiac determinants of natriuretic peptide levels
- What is the value of B-type natriuretic peptide testing for diagnosis, prognosis or monitoring of critically ill adult patients in intensive care?
- Natriuretic peptide testing in primary care patients
- Natriuretic peptide testing in emergency settings
- Minireviews
- Oxidative stress, free radicals and bone remodeling
- Plasma homocysteine and vascular disease in elderly patients with mental illness
- Opinion Papers
- Fate of abstracts presented at the 2002 IFCC meeting
- Transition from congress abstract to full paper: the case of a national Argentinean congress in clinical laboratory
- Genetics and Molecular Diagnostics
- Association of endothelin-1 gene polymorphisms with variant angina in Korean patients
- Single nucleotide polymorphisms in ABCG5 and ABCG8 genes in Chilean subjects with polygenic hypercholesterolemia and controls
- Paternal exclusion: allele sharing in microsatellite testing
- General Clinical Chemistry
- Rapid sample preparation and simultaneous quantitation of prostaglandins and lipoxygenase derived fatty acid metabolites by liquid chromatography-mass spectrometry from small sample volumes
- Plasma bilirubin correlations in non-obstructive cholestasis after partial hepatectomy
- Aggregation of lipoprotein and inflammatory parameters in families with a history of premature myocardial infarction: the Tallinn Myocardial Infarction Study
- Significant elevation of a Th2 cytokine, interleukin-10, in pelvic inflammatory disease
- Hemoglobin A1c determination in the A1C-Derived Average Glucose (ADAG) study
- The effect of the mode of delivery on maternal-neonatal interleukin-6, biogenic amine and their precursor amino acid concentrations
- A rapid liquid chromatography-tandem mass spectrometry analysis of whole blood sirolimus using turbulent flow technology for online extraction
- Validation and Outcome Studies
- Benefits of the iQ200 automated urine microscopy analyser in routine urinalysis
- Electrochemical detection of blood alcohol concentration using a disposable biosensor based on screen-printed electrode modified with Nafion and gold nanoparticles
- About the z-multiplier in total error calculations
- Letters to the Editor
- A hypothyroid patient with increased free thyroid hormones
- Evaluation of blood collection tubes specific for homocysteine measurement
- Influence of assay-dependent variability of serum insulin levels on insulin sensitivity indices
- Frequency and type of preanalytical errors in a laboratory medicine department in India
- Sample dilution causes a positive bias on C-reactive protein using VITROS reagents, diluents and instruments – clinical implications?
Articles in the same Issue
- Editorial
- Biochemical markers in clinical cardiology: perspectives from present to future. 1st IFCC-Ortho Clinical Diagnostics Conference on Clinical Diagnosis and the Clinical Laboratory
- Highlight: Cardiovascular Biomarkers
- Reviews
- The clinical impact of the universal diagnosis of myocardial infarction
- Troponin revisited 2008: assay performance
- Standardization of troponin I measurements: an update
- Biochemistry of B-type natriuretic peptide – where are we now?
- Clinical relevance of non-cardiac determinants of natriuretic peptide levels
- What is the value of B-type natriuretic peptide testing for diagnosis, prognosis or monitoring of critically ill adult patients in intensive care?
- Natriuretic peptide testing in primary care patients
- Natriuretic peptide testing in emergency settings
- Minireviews
- Oxidative stress, free radicals and bone remodeling
- Plasma homocysteine and vascular disease in elderly patients with mental illness
- Opinion Papers
- Fate of abstracts presented at the 2002 IFCC meeting
- Transition from congress abstract to full paper: the case of a national Argentinean congress in clinical laboratory
- Genetics and Molecular Diagnostics
- Association of endothelin-1 gene polymorphisms with variant angina in Korean patients
- Single nucleotide polymorphisms in ABCG5 and ABCG8 genes in Chilean subjects with polygenic hypercholesterolemia and controls
- Paternal exclusion: allele sharing in microsatellite testing
- General Clinical Chemistry
- Rapid sample preparation and simultaneous quantitation of prostaglandins and lipoxygenase derived fatty acid metabolites by liquid chromatography-mass spectrometry from small sample volumes
- Plasma bilirubin correlations in non-obstructive cholestasis after partial hepatectomy
- Aggregation of lipoprotein and inflammatory parameters in families with a history of premature myocardial infarction: the Tallinn Myocardial Infarction Study
- Significant elevation of a Th2 cytokine, interleukin-10, in pelvic inflammatory disease
- Hemoglobin A1c determination in the A1C-Derived Average Glucose (ADAG) study
- The effect of the mode of delivery on maternal-neonatal interleukin-6, biogenic amine and their precursor amino acid concentrations
- A rapid liquid chromatography-tandem mass spectrometry analysis of whole blood sirolimus using turbulent flow technology for online extraction
- Validation and Outcome Studies
- Benefits of the iQ200 automated urine microscopy analyser in routine urinalysis
- Electrochemical detection of blood alcohol concentration using a disposable biosensor based on screen-printed electrode modified with Nafion and gold nanoparticles
- About the z-multiplier in total error calculations
- Letters to the Editor
- A hypothyroid patient with increased free thyroid hormones
- Evaluation of blood collection tubes specific for homocysteine measurement
- Influence of assay-dependent variability of serum insulin levels on insulin sensitivity indices
- Frequency and type of preanalytical errors in a laboratory medicine department in India
- Sample dilution causes a positive bias on C-reactive protein using VITROS reagents, diluents and instruments – clinical implications?
