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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3525541?pdf=render |
| _version_ | 1818081754021363712 |
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| author | Fernando L Martin S Jeson Sangaralingham Brenda K Huntley Paul M McKie Tomoko Ichiki Horng H Chen Josef Korinek Gerald E Harders John C Burnett |
| author_facet | Fernando L Martin S Jeson Sangaralingham Brenda K Huntley Paul M McKie Tomoko Ichiki Horng H Chen Josef Korinek Gerald E Harders John C Burnett |
| author_sort | Fernando L Martin |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T19:11:13Z |
| format | Article |
| id | doaj.art-4a4961a497004f00ba22fb4c98d3337a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T19:11:13Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4a4961a497004f00ba22fb4c98d3337a2022-12-22T01:36:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5242210.1371/journal.pone.0052422CD-NP: a novel engineered dual guanylyl cyclase activator with anti-fibrotic actions in the heart.Fernando L MartinS Jeson SangaralinghamBrenda K HuntleyPaul M McKieTomoko IchikiHorng H ChenJosef KorinekGerald E HardersJohn C BurnettNatriuretic 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.http://europepmc.org/articles/PMC3525541?pdf=render |
| spellingShingle | Fernando L Martin S Jeson Sangaralingham Brenda K Huntley Paul M McKie Tomoko Ichiki Horng H Chen Josef Korinek Gerald E Harders John C Burnett CD-NP: a novel engineered dual guanylyl cyclase activator with anti-fibrotic actions in the heart. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3525541?pdf=render |
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