Three molecular forms of atrial natriuretic peptides: quantitative analysis and biological characterization

Abstract

Atrial natriuretic peptide (ANP) is primarily produced in the heart tissue and plays a pivotal role in maintaining cardiovascular homeostasis in endocrine and autocrine/paracrine systems and has clinical applications as a biomarker and a therapeutic agent for cardiac diseases. ANP is synthesized by atrial cardiomyocytes as a preprohormone that is processed by a signal peptidase and stored in secretory granules as a prohormone. Subsequent proteolytic processing of ANP by corin during the secretion process results in a bioactive form consisting of 28 amino acid residues. Mechanical stretch of the atrial wall and multiple humoral factors directly stimulates the transcription and secretion of ANP. Secreted ANP elicits natriuretic and diuretic effects via cyclic guanosine monophosphate produced through binding to the guanylyl cyclase-A/natriuretic peptide receptor-A. Circulating ANP is subjected to rapid clearance by a natriuretic peptide receptor-C-mediated mechanism and proteolytic degradation by neutral endopeptidase. In humans, ANP is present as three endogenous molecular forms: bioactive α-ANP, a homodimer of α-ANP designated as β-ANP, and an ANP precursor designated as proANP (also referred to as γ-ANP). The proANP and especially β-ANP, as minor forms in circulation, are notably increased in patients with cardiac diseases, suggesting the utility of monitoring the pathophysiological conditions that result in abnormal proANP processing that cannot be monitored by inactive N-terminal proANP-related fragments. Emerging plate-based sandwich immunoassays for individual quantitation of the three ANP forms enables evaluation of diagnostic implications and net ANP bioactivity. This new tool may provide further understanding in the pathophysiology of cardiac diseases. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

SLC39A8 gene encoding a metal ion transporter: discovery and bench to bedside

“…In a Sglt2>Cre>Slc39a8 ( flox / neo ) conditional knockout in which renal epithelial Slc39a8 expression was ablated, atrial natriuretic peptide (ANP) levels were markedly decreased (Jorge-Nebert L, Soleimani M, and Nebert DW, unpublished). ANPs are known to dilate blood vessels and induce natriuresis and diuresis—resulting in lowered blood pressure and blood volume; in part, ANPs counterbalance actions of the renin-angiotensin-aldosterone and neurohormonal systems, thereby playing a pivotal role in cardiovascular regulation [77]. In Slc39a8 ( neo / neo ) liver, angiotensin-1-converting enzyme-2 ( Ace2 ) was also upregulated [28], perhaps helping to explain the potential clinical role of SLC39A8 in heart disease.…”

The Natriuretic Peptide System: A Single Entity, Pleiotropic Effects

“…In cases of severe heart failure, it is also possible to detect high plasma levels of β-ANP, which is an anti-parallel dimer of α-ANP. However, it is still not clear as to the precise mechanism that regulates its formation and secretion [6].…”

Natriuretic Peptides: The Case of Prostate Cancer

“…The anti-inflammatory and immune-modulatory effects of ANP, besides being related to NF-κB inhibition [ 24 , 30 , 31 , 32 , 33 ], are therefore linked to NALP3-inflammasome platform. Given that the ANP-dependent biological responses occur via its binding to NPRA, expressed in different type of immune cells [ 34 ], it has been reasonably suggested that, by autocrine/paracrine mechanisms [ 24 , 35 ], ANP exerts anti-inflammatory and immune-modulatory effects in the tissue microenvironment [ 20 ]. A similar biological effect based on similar molecular mechanisms, i.e., NF-κB and NALP3/ASC/Caspase-1 cascade inhibition, has been recently described for BNP [ 36 ], further supporting the anti-inflammatory role of this peptide [ 8 , 13 , 32 , 37 , 38 , 39 , 40 , 41 ].…”