Key result
Dipeptidyl-peptidase IV cleaves BNP(1-32) into BNP(3-32), which exerts less natriuretic and diuretic effects in vivo, suggesting DPP IV inhibitors could potentially benefit heart failure patients.
Why the study?
Does DPP IV cleavage of BNP(1-32) to BNP(3-32) alter its biological effects?
Does DPP IV cleavage of BNP(1-32) to BNP(3-32) alter its biological effects?
DPP IV cleaves active BNP(1-32) into BNP(3-32), which has reduced diuretic and vasodilatory effects in vivo, suggesting DPP IV inhibition could potentially increase active BNP bioavailability in heart failure.
DPP-IV inhibition may enhance BNP activity in HF; hypothesis-generating and should not yet change practice.
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.
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Vanderheyden et al. (2009) conducted a review in Congestive heart failure. Dipeptidyl-peptidase IV (DPP IV) was evaluated. Dipeptidyl-peptidase IV cleaves BNP(1-32) into BNP(3-32), which exerts less natriuretic and diuretic effects in vivo, suggesting DPP IV inhibitors could potentially benefit heart failure patients.
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