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CD-NP: A Novel Engineered Dual Guanylyl Cyclase Activator with Anti-Fibrotic Actions in the Heart

Natriuretic peptides (NPs) are cardioprotective through the activation of guanylyl cyclase (GC) receptors A and B. CD-NP, also known as cenderitide, is a novel engineered NP that was designed to uniquely serve as a first-in-class dual GC receptor agonist. Recognizing the aldosterone suppressing acti...

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Autores principales: Martin, Fernando L., Sangaralingham, S. Jeson, Huntley, Brenda K., McKie, Paul M., Ichiki, Tomoko, Chen, Horng H., Korinek, Josef, Harders, Gerald E., Burnett, John C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525541/
https://www.ncbi.nlm.nih.gov/pubmed/23272242
http://dx.doi.org/10.1371/journal.pone.0052422
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author Martin, Fernando L.
Sangaralingham, S. Jeson
Huntley, Brenda K.
McKie, Paul M.
Ichiki, Tomoko
Chen, Horng H.
Korinek, Josef
Harders, Gerald E.
Burnett, John C.
author_facet Martin, Fernando L.
Sangaralingham, S. Jeson
Huntley, Brenda K.
McKie, Paul M.
Ichiki, Tomoko
Chen, Horng H.
Korinek, Josef
Harders, Gerald E.
Burnett, John C.
author_sort Martin, Fernando L.
collection PubMed
description Natriuretic peptides (NPs) are cardioprotective through the activation of guanylyl cyclase (GC) receptors A and B. CD-NP, also known as cenderitide, is a novel engineered NP that was designed to uniquely serve as a first-in-class dual GC receptor agonist. Recognizing the aldosterone suppressing actions of GC-A activation and the potent inhibitory actions on collagen synthesis and fibroblast proliferation through GC-B activation, the current study was designed to establish the anti-fibrotic actions of CD-NP, administered subcutaneously, in an experimental rat model of early cardiac fibrosis induced by unilateral nephrectomy (UNX). Our results demonstrate that a two week subcutaneous infusion of CD-NP significantly suppresses left ventricular fibrosis and circulating aldosterone, while preserving both systolic and diastolic function, in UNX rats compared to vehicle treated UNX rats. Additionally we also confirmed, in vitro, that CD-NP significantly generates the second messenger, cGMP, through both the GC-A and GC-B receptors. Taken together, this novel dual GC receptor activator may represent an innovative anti-fibrotic therapeutic agent.
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spelling pubmed-35255412012-12-27 CD-NP: A Novel Engineered Dual Guanylyl Cyclase Activator with Anti-Fibrotic Actions in the Heart Martin, Fernando L. Sangaralingham, S. Jeson Huntley, Brenda K. McKie, Paul M. Ichiki, Tomoko Chen, Horng H. Korinek, Josef Harders, Gerald E. Burnett, John C. PLoS One Research Article Natriuretic peptides (NPs) are cardioprotective through the activation of guanylyl cyclase (GC) receptors A and B. CD-NP, also known as cenderitide, is a novel engineered NP that was designed to uniquely serve as a first-in-class dual GC receptor agonist. Recognizing the aldosterone suppressing actions of GC-A activation and the potent inhibitory actions on collagen synthesis and fibroblast proliferation through GC-B activation, the current study was designed to establish the anti-fibrotic actions of CD-NP, administered subcutaneously, in an experimental rat model of early cardiac fibrosis induced by unilateral nephrectomy (UNX). Our results demonstrate that a two week subcutaneous infusion of CD-NP significantly suppresses left ventricular fibrosis and circulating aldosterone, while preserving both systolic and diastolic function, in UNX rats compared to vehicle treated UNX rats. Additionally we also confirmed, in vitro, that CD-NP significantly generates the second messenger, cGMP, through both the GC-A and GC-B receptors. Taken together, this novel dual GC receptor activator may represent an innovative anti-fibrotic therapeutic agent. Public Library of Science 2012-12-18 /pmc/articles/PMC3525541/ /pubmed/23272242 http://dx.doi.org/10.1371/journal.pone.0052422 Text en © 2012 Martin et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Martin, Fernando L.
Sangaralingham, S. Jeson
Huntley, Brenda K.
McKie, Paul M.
Ichiki, Tomoko
Chen, Horng H.
Korinek, Josef
Harders, Gerald E.
Burnett, John C.
CD-NP: A Novel Engineered Dual Guanylyl Cyclase Activator with Anti-Fibrotic Actions in the Heart
title CD-NP: A Novel Engineered Dual Guanylyl Cyclase Activator with Anti-Fibrotic Actions in the Heart
title_full CD-NP: A Novel Engineered Dual Guanylyl Cyclase Activator with Anti-Fibrotic Actions in the Heart
title_fullStr CD-NP: A Novel Engineered Dual Guanylyl Cyclase Activator with Anti-Fibrotic Actions in the Heart
title_full_unstemmed CD-NP: A Novel Engineered Dual Guanylyl Cyclase Activator with Anti-Fibrotic Actions in the Heart
title_short CD-NP: A Novel Engineered Dual Guanylyl Cyclase Activator with Anti-Fibrotic Actions in the Heart
title_sort cd-np: a novel engineered dual guanylyl cyclase activator with anti-fibrotic actions in the heart
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525541/
https://www.ncbi.nlm.nih.gov/pubmed/23272242
http://dx.doi.org/10.1371/journal.pone.0052422
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