title: 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.
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nagai-Okatani
authors.affiliation: National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: Kenji
authors.identifier: http://orcid.org/0000-0003-4784-5599
authors.initials: K
authors.lastname: Kangawa
authors.affiliation: Omics Research Center, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Naoto
authors.identifier: http://orcid.org/0000-0002-9913-1144
authors.initials: N
authors.lastname: Minamino
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay; D032383:Myocytes, Cardiac / Q000378:metabolism; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism
chemical_list: D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A
keywords: atrial natriuretic peptide; biomarker; cardiac diseases; molecular form; natriuretic peptide family; peptide quantitation