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- Basic science
- chronic heart failure
- coronary artery disease
- endothelial function
- heart failure
- natriuretic peptides
During the past decade the measurement of B-type natriuretic peptide (BNP) and the N-terminal fragment of proBNP (NT-proBNP) has become a widely used tool for diagnosing heart failure.1 In their paper published in this issue of Heart, Nishikimi and coworkers2 (see page 152), from the group of Kazuwa Nakao, report that most endogenous NT-proBNP found in the circulation is glycosylated and thus undetectable with current assay systems. These findings are both surprising and intriguing and could have substantial clinical implications, in particular if the degree of glycosylation is found to vary according to the severity of disease.
BNP was originally discovered in porcine brain and termed ‘brain natriuretic peptide’, but early pioneer work of Saito et al,3 from the group of Nakao and Imura, linked BNP production to the heart. By examining BNP production throughout the body, the heart was identified as the principal organ for BNP production and the protein was later renamed ‘B-type natriuretic peptide’.1 In 1991 the same group, by examining BNP content in failing explanted hearts and measuring BNP levels in the coronary sinus and proximal aorta, identified the ventricles as the primary source of circulating BNP in patients with heart failure.4
Translation of the BNP gene results in the formation of a 134 amino acid precursor peptide, pre-proBNP. Following removal of the signal sequence, a 108 amino acid prohormone, proBNP1–108 (subscript indicative of amino acid composition), is formed. In the mid-1990s assays directed at epitopes in the N-terminal portion of the pro-hormone (NT-proBNP) were developed, and a model of intracellular cleavage of proBNP1–108 into two fragments, ie, NT-proBNP (proBNP1–76) and BNP1–32 (eg, proBNP77–108) in a 1:1 fashion was advanced.1 This model seemed …
Linked article 300102.
Competing interests During the past 3 years, TO has received speaker's honoraria from Abbott Laboratories and Roche Diagnostics, manufacturers of assays for BNP and NT-proBNP. TO and HR have an ongoing research collaboration with HyTest Ltd, manufacturer of assays for BNP and NT-proBNP measurement.
Provenance and peer review Commissioned; internally peer reviewed.
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