Processing of Pro–B-Type Natriuretic Peptide: Furin and Corin as Candidate Convertases2

Abstract

BACKGROUND: B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are the products of the enzyme-mediated cleavage of their precursor molecule, proBNP. The clinical significance of proBNP-derived peptides as biomarkers of heart failure has been explored thoroughly, whereas little is known about the mechanisms of proBNP processing. We investigated the role of 2 candidate convertases, furin and corin, in human proBNP processing.

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

“…ANP is secreted from cardiomyocytes as active hormone, whereas BNP is secreted from cardiomyocytes as a 108‐amino‐acid prohormone (proBNP). In circulation, glycosylated proBNP is gradually deglycosylated and further processed by the proNP convertases, corin or furin, to inactive NT‐proBNP1‐76 and active BNP1‐32 7. Evolutionary studies suggest that CNP, which, differently from ANP and BNP, does not stimulate natriuresis, is the most ancient family member.…”

Natriuretic Peptides and Analytical Barriers

“…The degree of glycosylation of both proBNP and NT-proBNP is highly individual. It is also known to inhibit the activity of furin on the 76 -78 amino acid cleavage site (21 ).…”

“…BNP can also be proteolyzed by insulindegrading enzyme (IDE), but not by NEP and IDE implying that another enzyme is involved in cleavage (25 ). BNP 4 -32 may be the result of corin activity (21 ). Another protease, peptidyl arginine aldehyde protease, can also degrade BNP, and meprin was shown to lyse BNP in animal models but not in humans (26 ).…”

A candidate liquid chromatography mass spectrometry reference method for the quantification of the cardiac marker 1-32 B-type natriuretic peptide

“…B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are cardiac biomarkers secreted as proBNP, the prohormone of BNP, by the myocytes of the left ventricle in response to volume overload in an event of congestive heart failure [1]. In 2012, specific age-independent decision cut-offs for both BNP (≤100 ng/L) and NT-proBNP (≤300 ng/L) were endorsed [2] and measurements of circulating BNP are currently used in clinical practice for the diagnosis of acute and chronic heart failure, risk stratification and monitoring response to therapy [3].…”