Exposing the High Heterogeneity of Circulating Pro B-Type Natriuretic Peptide Fragments in Healthy Individuals and Heart Failure Patients.
Clin Chem
; 66(9): 1200-1209, 2020 09 01.
Article
em En
| MEDLINE
| ID: mdl-32797158
ABSTRACT
BACKGROUND:
The high molecular complexity of variably O-glycosylated and degraded pro B-type natriuretic peptide (proBNP) derived molecular forms challenges current immunoassays. Antibodies used show pronounced differences in cross-reactivities with these circulating fragments, which still need to be better characterized on a molecular level. To pave the way for advanced quantitative assays in the future, it is critical to fully understand these circulating forms.METHODS:
Plasma samples were collected from 8 heart failure (HF) patients and 2 healthy controls. NT-proBNP and proBNP were purified by immunoprecipitation and analyzed by nano-flow liquid chromatography coupled to high-resolution mass spectrometry. Fragments formed during proteolysis in solution digestion were distinguished from naturally occurring peptides by using an 18O stable isotope labeling strategy.RESULTS:
We detected 16 previously unknown circulating fragments of proBNP peptides (9 of which are located in the N-terminal and 7 in the C-terminal region), revealing a more advanced state of degradation than previously known. Two of these fragments are indicative of either unidentified processing modes or a far-reaching C-terminal degradation (or a combination thereof) of the precursor proBNP.CONCLUSIONS:
Our results further restrict ideal target epitopes for immunoassay antibodies and expand the current thinking of diversity, degradation, and processing of proBNP, as well as the distribution of circulating forms.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Peptídeo Natriurético Encefálico
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Insuficiência Cardíaca
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Chem
Assunto da revista:
QUIMICA CLINICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Áustria