Accessible Requires Authentication Published by De Gruyter March 1, 2009

Dipeptidyl-peptidase IV and B-type natriuretic peptide. From bench to bedside

Marc Vanderheyden, Jozef Bartunek, Marc Goethals, Sofie Verstreken, Anne-Marie Lambeir, Ingrid De Meester and Simon Scharpé

Abstract

B-type natriuretic peptide (BNP) has emerged as a reliable biomarker in patients with congestive heart failure. The mature, biologically active B-type natriuretic peptide, BNP(1–32), is cleaved by corin from the 108 amino acid proBNP. However, in vivo as well as in vitro data demonstrated that this BNP(1–32) might be an ideal substrate for the endogenous aminopeptidase, dipeptidyl-peptidase IV (DPP IV). DPP IV removes the two amino terminal amino acids (Ser Pro) from BNP(1–32) to produce BNP(3–32), which has been detected in plasma of patients with congestive heart failure. The biological effects of BNP(3–32) remain undetermined. In cultured human cardiomyocytes and fibroblasts, equimolar concentrations of BNP(1–32) and BNP(3–32) both exert similar biological effects, as evidenced by their cGMP (cyclic guanylate monophosphate) generating capacity. However, in a canine model, intravenous BNP(3–32) infusion resulted in less natriuresis, diuresis, and vasodilation compared to intravenous infusion of BNP(1–32). The clinical relevance of these observations might be important for patients in whom the plasma BNP concentrations, measured by commercially available immunoassays, are high. Further studies exploring whether DPP IV inhibitors increase the bioavailability of BNP(1–32), delay the progression of heart failure, and increase the efficacy of exogenous administration of BNP(1–32) in decompensated heart failure are needed.

Clin Chem Lab Med 2009;47:248–52.


Corresponding author: Marc Vanderheyden, Cardiovascular Center, Onze Lieve Vrouwziekenhuis, Moorselbaan 164, 9300 Aalst, Belgium Phone: +32-53-724439,

Received: 2008-10-8
Accepted: 2009-1-19
Published Online: 2009-03-01
Published in Print: 2009-03-01

©2009 by Walter de Gruyter Berlin New York