ArticleScientific reports2016
Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 97 citations in OpenAlex.
- Neprilysin mediated cleavage of phospholamban dysregulates SERCA in heart failure.bioRxiv : the preprint server for biology · 2026Article
- Prognostic value of plasma cortisol concentration in dogs with congestive heart failure.Journal of veterinary internal medicine · 2026Article
- Fulacimstat Reduces Angiotensin II in Kidney Allografts in a Cross-Sectional Exploratory Study.Kidney international reports · 2026Article
- The joint-local renin-angiotensin system in rheumatoid arthritis and osteoarthritis: mechanistic evidence, disease-specific patterns, and translational perspectives.Rheumatology international · 2026Review
- Upregulation of angiotensin-(1-7) formation in human podocytes - enzyme activity assay upon fluid flow shear stress.PloS one · 2026Article
- Combined RAS Modulation: The Effect on Plasma and Tissue Angiotensin Peptide Levels.Physiological research · 2025Article
- Fenofibrate as a Modulator of the Renin-Angiotensin System in Su/Hx-Induced Pulmonary Arterial Hypertension.International journal of molecular sciences · 2025Article
- Cullin-3 regulates the renal baroreceptor machinery that controls renin gene expression.JCI insight · 2025Article
- Post hoc comparison of the intrarenal and circulating renin-angiotensin(-aldosterone) systems in cats with ischemia-induced chronic kidney disease.Physiological reports · 2025Article
- Angiotensin Dysregulation in Patients with Arterial Aneurysms.International journal of molecular sciences · 2025Article
- The Role of Renin-Angiotensin System in Diabetic Nephropathy: An Update.Mini reviews in medicinal chemistry · 2025Review
- Insulin restores renal neprilysin (NEP) and attenuates the shedding of urinary NEP and KIM-1 in diabetic Akita mice.Frontiers in pharmacology · 2025Article
- Preclinical modeling of metabolic syndrome to study the pleiotropic effects of novel antidiabetic therapy independent of obesity.Scientific reports · 2024Article
- Mathematical modelling of the influence ofHeliyon · 2024Article
- Alternative Renin-Angiotensin System.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Article
- Comprehensive review on neprilysin (NEP) inhibitors: design, structure-activity relationships, and clinical applications.Frontiers in pharmacology · 2024Review
- Angiotensin receptor blockers, but not angiotensin-converting enzyme inhibitors, inhibit abnormal bone changes in spondyloarthritis.Experimental & molecular medicine · 2023Article
- The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Dose-response of benazepril on biomarkers of the classical and alternative pathways of the renin-angiotensin-aldosterone system in dogs.Scientific reports · 2023Article
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Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
Abstract
Cardiovascular and renal pathologies are frequently associated with an activated renin-angiotensin-system (RAS) and increased levels of its main effector and vasoconstrictor hormone angiotensin II (Ang II). Angiotensin-converting-enzyme-2 (ACE2) has been described as a crucial enzymatic player in shifting the RAS towards its so-called alternative vasodilative and reno-protective axis by enzymatically converting Ang II to angiotensin-(1-7) (Ang-(1-7)). Yet, the relative contribution of ACE2 to Ang-(1-7) formation in vivo has not been elucidated. Mass spectrometry based quantification of angiotensin metabolites in the kidney and plasma of ACE2 KO mice surprisingly revealed an increase in Ang-(1-7), suggesting additional pathways to be responsible for alternative RAS activation in vivo. Following assessment of angiotensin metabolism in kidney homogenates, we identified neprilysin (NEP) to be a major source of renal Ang-(1-7) in mice and humans. These findings were supported by MALDI imaging, showing NEP mediated Ang-(1-7) formation in whole kidney cryo-sections in mice. Finally, pharmacologic inhibition of NEP resulted in strongly decreased Ang-(1-7) levels in murine kidneys. This unexpected new role of NEP may have implications for the combination therapy with NEP-inhibitors and angiotensin-receptor-blockade, which has been shown being a promising therapeutic approach for heart failure therapy.
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