Different Susceptibility of B-Type Natriuretic Peptide (BNP) and BNP Precursor (proBNP) to Cleavage by Neprilysin: The N-Terminal Part Does Matter

Semenov, Alexander G.; Katrukha, Alexey G.

doi:10.1373/clinchem.2016.254524

Cited by 44 publications

(26 citation statements)

References 32 publications

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“…We do not know how representative the changes in NTproBNP with this novel agent are compared to other agents. In addition, it may be after additional studies that metrics about how to use BNP assays will be developed (38,39 ). Increases in circulating BNP might inhibit proBNP production, thus decreases in the NT-proBNP concentration might not be due to improvements in cardiac function.…”

Section: Analytics Of Natriuretic Peptide Assaysmentioning

confidence: 99%

Natriuretic Peptides and Analytical Barriers

Vasile

Jaffe

2017

Clinical Chemistry

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BACKGROUND:The natriuretic peptide system is an endocrine, autocrine and paracrine system that plays an important role in the maintenance of cardiovascular homeostasis. Biomarkers based on these peptides are important diagnostic and prognostic tools for myocardial function.CONTENT: Although natriuretic peptides were discovered more than 2 decades ago, their intricate and complex biology is associated with important questions not yet elucidated. The diversity of circulating forms of natriuretic peptides, the distinct expression of these forms in particular patients, and the heterogeneity of heart failure forms, along with specific assay-related and preanalytic issues, cause assays to be poorly harmonized.

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Section: Analytics Of Natriuretic Peptide Assaysmentioning

confidence: 99%

Natriuretic Peptides and Analytical Barriers

Vasile

Jaffe

2017

Clinical Chemistry

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“…ProBNP, a 108‐amino acid polypeptide, is synthesized and cut into a 76‐amino acid non‐biologically active peptide [N‐terminal proBNP (NT‐proBNP)] and a 32‐amino acid biologically active peptide (BNP) in cardiomyocytes. Neprilysin was shown to be responsible for NP degradation such as atrial NP and C‐type NP, but has neither effect on proBNP nor on NT‐proBNP . As sacubitril acts inhibiting neprilysin activity, it was thought that it would induce an initial rise, followed by a decline, in NP like BNP, while lowering NT‐proBNP levels, as seen in the PARADIGM‐HF and PIONEER‐HF trials .…”

Section: Baseline Characteristics Of the Study Patients (N = 70)mentioning

confidence: 99%

Sacubitril/valsartan and B‐type natriuretic peptide value: recalculating route

Abellas-Sequeiros

Díaz

Rey³

et al. 2019

European J of Heart Fail

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“…It is in this context that Semenov and Katrukha performed a set of in vitro experiments focused on the effects of neprilysin on BNP and proBNP (6 ). In their work published in the April issue of Clinical Chemistry, the authors incubated BNP and proBNP with neprilysin.…”

Section: Open Questions About Bnp and Neprilysin Inhibitionmentioning

confidence: 99%

B-Type Natriuretic Peptide Testing in the Era of Neprilysin Inhibition: Are the Winds of Change Blowing?

Januzzi

2016

Clinical Chemistry

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There is nothing permanent except change.- Heraclitus of EphesusThe care of patients with heart failure (HF) 2 and reduced ejection fraction has traditionally included therapies resulting in inhibition of the renin-angiotensin-aldosterone system; specifically, current clinical practice guidelines articulate use of either angiotensin converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) as first-line therapy for patients with HF and left ventricular ejection fraction Ͻ40% (1 ). Accordingly, the use of ACEi or ARB therapy for such patients had been viewed as a foundation of HF care until recently.In spring 2014, however, the medical community received startling news of the premature suspension of the Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF). The trial was suspended because of overwhelming evidence that treatment of HF and reduced ejection fraction with the combination ARB (valsartan)/neprilysin inhibitor (sacubitril) resulted in substantial reduction in a wide array of cardiovascular complications compared with the gold standard ACEi comparator, enalapril.The magnitude of benefit from valsartan/sacubitril is hard to overstate: compared with well-dosed ACEi therapy, those treated with neprilysin inhibition in the PARADIGM-HF trial experienced 20% reduction in cardiovascular death or hospitalization for HF (P ϭ 4.0 ϫ 10 Ϫ7 ) and 16% reduction in all-cause mortality (P Ͻ 0.001) (2 ). Results such as those from PARADIGM-HF are a rarity in HF trials, where development of new classes of therapeutics has been challenging. Why Inhibit Neprilysin?Neprilysin is a neutral endopeptidase that is responsible for the degradation of several endogenous vasoactive substances, including natriuretic peptides [atrial natriuretic peptide, B-type natriuretic peptide (BNP), and C-type natriuretic peptide], bradykinin, and adrenomedullin. Given that neprilysin degrades vascular peptides, its blockade results in a net vasodilatory effect, potentiated by its combination with an ACEi or ARB; conceptually, by inhibiting neprilysin together with inhibition of the renin-angiotensin-aldosterone system, greater amelioration of neurohormonal activation, vasoconstriction, sodium retention, and ventricular remodeling would occur. Effects of Neprilysin Inhibition on the BNP FamilyIn vitro studies suggest that neprilysin cleaves BNP in several regions (3 ). As neprilysin degrades epitopes recognized by standard immunoassays for BNP, recovery of the peptide decreases. Accordingly, neprilysin inhibition predictably results in an increase of BNP concentrations (4 ): in PARADIGM-HF, concentrations of plasma BNP (measured by using the Advia Centaur assay) increased on average by 50 pg/mL from a baseline median concentration of 255 pg/mL (5 ). After 8 months, median BNP concentrations in those treated with neprilysin inhibition were lower than at 4 weeks in PARADIGM-HF, tempting one to suggest that increased ...

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Different Susceptibility of B-Type Natriuretic Peptide (BNP) and BNP Precursor (proBNP) to Cleavage by Neprilysin: The N-Terminal Part Does Matter

Cited by 44 publications

References 32 publications

Natriuretic Peptides and Analytical Barriers

Natriuretic Peptides and Analytical Barriers

Sacubitril/valsartan and B‐type natriuretic peptide value: recalculating route

B-Type Natriuretic Peptide Testing in the Era of Neprilysin Inhibition: Are the Winds of Change Blowing?

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