Neprilysin 2 catalyses the degradation of natriuretic peptides despite sacubitrilat Inhibition.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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.
What This Study Doesn't 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.
Trust & Context
- Original Title:
- Neprilysin 2 catalyses the degradation of natriuretic peptides despite sacubitrilat Inhibition.
- Published In:
- Scientific reports, 15(1), 27401 (2025)
- Authors:
- Selezneva, Elizaveta M, Feygina, Evgeniya E, Ageeva, Liudmila V, Rozov, Fedor N, Kopylova, Irina V, Altshuler, Evgeny P, Semenov, Alexander G
- Database ID:
- RPEP-13503
Evidence Hierarchy
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Cite This Study
https://rethinkpeptides.com/research/RPEP-13503APA
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
MLA
Selezneva, Elizaveta M, et al. "Neprilysin 2 catalyses the degradation of natriuretic peptides despite sacubitrilat Inhibition.." Scientific reports, 2025. https://doi.org/10.1038/s41598-025-10166-z
RethinkPeptides
RethinkPeptides Research Database. "Neprilysin 2 catalyses the degradation of natriuretic peptid..." RPEP-13503. Retrieved from https://rethinkpeptides.com/research/selezneva-2025-neprilysin-2-catalyses-the
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.