This record provides bibliographic details and links to the original research. An editorial study breakdown is not available.
What the researchers found
Neprilysin 2 (NEP2), a close relative of neprilysin, degrades natriuretic peptides ANP and BNP but is NOT blocked by sacubitrilat, the active form of the heart failure drug sacubitril. NEP2 is expressed in heart cells and blood vessel cells.
Why it matters
Heart failure patients take sacubitril to preserve natriuretic peptides. If NEP2 continues to break them down despite treatment, it could limit the drug's effectiveness. This reveals a potential therapeutic gap.
The numbers in context
NEP2 and NEP mRNA detected in cardiomyocytes and endothelial cells. NEP2 cleaved ANP and BNP. NEP2 was insensitive to sacubitrilat. NEP2 (but not NEP) cleaved proBNP to truncated form (amino acids 5-32).
How the study worked
RT-PCR for NEP and NEP2 expression in cardiovascular cells. In vitro cleavage assays using recombinant NEP and NEP2 soluble domains. Sandwich immunoassays with antibodies specific for proteolytic epitopes. Tested sacubitrilat inhibition.
Who was studied
Recombinant enzymes and cardiovascular cell lines
What this study cannot tell us
In vitro study. NEP2 protein expression and activity in vivo not confirmed. Relevance to clinical heart failure outcomes is theoretical. Studied concentrations may not reflect physiological conditions.
Read the original research
Neprilysin 2 catalyses the degradation of natriuretic peptides despite sacubitrilat Inhibition.
Scientific reports, 15(1), 27401
Citation
Selezneva, Elizaveta M; Feygina, Evgeniya E; Ageeva, Liudmila V; Rozov, Fedor N; Kopylova, Irina V; Altshuler, Evgeny P; Semenov, Alexander G. (2025). Neprilysin 2 catalyses the degradation of natriuretic peptides despite sacubitrilat Inhibition.. Scientific reports, 15(1), 27401. https://doi.org/10.1038/s41598-025-10166-z