Detection of Neprilysin-Derived BNP Fragments in the Circulation: Possible Insights for Targeted Neprilysin Inhibition Therapy for Heart Failure

B-type natriuretic peptides, or BNP, and N-terminal proBNP, or NT-proBNP, are peptides produced in the heart in response to increased wall stretch and volume overload.  Their production and secretion increases in the heart with the progression of heart failure and they have emerged as useful heart failure biomarkers.  Since the discovery of BNPs in the 1980s, much effort has been made to precisely determine the BNP and NT-proBNP levels via immunoassays for reliable heart failure diagnostics. Entresto™ is a new heart failure therapy that includes sacubitril as one of its components.  Sacubitril is a specific inhibitor of neprilysin. This is a zinc-dependent metalloproteinase that cleaves various peptides including BNP.  In fact, augmentation of circulating BNP due to neprilysin inhibition is considered as a possible mechanism of Entresto’s positive effects.  A paper appearing in the October 2019 issue of Clinical Chemistry examines the circulating products of BNP proteolysis by neprilysin and how they might reflect impact on the metabolism of active BNP.