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. 2023 May 8;44(3):379-392.
doi: 10.1210/endrev/bnac029.

A State of Natriuretic Peptide Deficiency

Michael Nyberg  1 , Dijana Terzic  2 , Trine P Ludvigsen  1 , Peter D Mark  2 , Natasha B Michaelsen  1 , Steen Z Abildstrøm  1 , Mads Engelmann  1 , A Mark Richards  3 , Jens P Goetze  2   4
Affiliations

A State of Natriuretic Peptide Deficiency

Michael Nyberg et al. Endocr Rev. .

Abstract

Measurement of natriuretic peptides (NPs) has proven its clinical value as biomarker, especially in the context of heart failure (HF). In contrast, a state of partial NP deficiency appears integral to several conditions in which lower NP concentrations in plasma presage overt cardiometabolic disease. Here, obesity and type 2 diabetes have attracted considerable attention. Other factors-including age, sex, race, genetics, and diurnal regulation-affect the NP "armory" and may leave some individuals more prone to development of cardiovascular disease. The molecular maturation of NPs has also proven complex, with highly variable O-glycosylation within the biosynthetic precursors. The relevance of this regulatory step in post-translational propeptide maturation has recently become recognized in biomarker measurement/interpretation and cardiovascular pathophysiology. An important proportion of people appear to have reduced effective net NP bioactivity in terms of receptor activation and physiological effects. The state of NP deficiency both entails a potential for further biomarker development and could also offer novel pharmacological possibilities. Alleviating the state of NP deficiency before development of overt cardiometabolic disease in selected patients could be a future path for improving precision medicine.

Keywords: ANP; BNP; CNP; hypertension; natriuretic peptide; obesity.

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Conflict of interest statement

Conflict of Interest M.N., T.P.L, N.B.M., S.Z.A., and M.E. are employees at Novo Nordisk. The company has no products relating to the current manuscript. J.P.G. has received an honorarium from Novo for advice on biomarker measurement. All other authors are university-affiliated and have no conflicts of interest to declare.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
The 3 NPs (human sequences) and their receptors.
Figure 2.
Figure 2.
(A) Cardiac ANP and BNP in mammalian physiology. Modified from Levin et al., New Engl. J. Med. (1998). (B) ProBNP expression in atrial and ventricular tissue. Note that proBNP is stored in normal atrial tissue while absent in ventricular myocytes. Taken from Goetze et al., FASEB J. (2004).
Figure 3.
Figure 3.
(A) General presentation of BNP gene expression (humans). The final products are considerably more heterogenous via post-translational modifications than shown here. (B) Comparison of proinsulin and proBNP as prostructures.
Figure 4.
Figure 4.
(A) The first published data on ANP as a novel plasma biomarker in cardiovascular disease. Modified from Burnett Jr et al., Science (1986). (B) A simplified presentation of the 2 main hormonal systems in HF. Inhibition of the RAAS system is today a hallmark of HF therapy, whereas stimulation or replacement of NPs is still an area for further exploration. (C) Presentation of diagnostic performance for a given biomarker. Note that the so-called “gray” zone lies between A and B. For NPs, clinical measurement may reside in this zone up to 40% of all prescribed tests. (D) Genetic mutation in human ANP gene leading to a C-terminal elongated peptide form.
Figure 5.
Figure 5.
Overview of factors involved in the state of NP deficiency.
See this image and copyright information in PMC

References

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