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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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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. |
format | Online Article Text |
id | pubmed-3525541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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