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

Fernando L. Martin, S Jeson Sangaralingham, Brenda K. Huntley, Paul McKie, Tomoko Ichiki, Horng Haur Chen, Josef Korinek, Gerald E. Harders, John C Jr. Burnett

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere52422
JournalPLoS One
Volume7
Issue number12
DOIs
StatePublished - Dec 18 2012

Fingerprint

natriuretic peptides
guanylate cyclase
Natriuretic Peptides
Guanylate Cyclase
heart
Guanylate Cyclase-Coupled Receptors
Rats
Chemical activation
aldosterone
receptors
Aldosterone
fibrosis
Fibrosis
Subcutaneous Infusions
Second Messenger Systems
Fibroblasts
Nephrectomy
second messengers
rats
peptide A

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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; Ichiki, Tomoko; Chen, Horng Haur; Korinek, Josef; Harders, Gerald E.; Burnett, John C Jr.

In: PLoS One, Vol. 7, No. 12, e52422, 18.12.2012.

Research output: Contribution to journalArticle

Martin, Fernando L. ; Sangaralingham, S Jeson ; Huntley, Brenda K. ; McKie, Paul ; Ichiki, Tomoko ; Chen, Horng Haur ; Korinek, Josef ; Harders, Gerald E. ; Burnett, John C Jr. / CD-NP : A Novel Engineered Dual Guanylyl Cyclase Activator with Anti-Fibrotic Actions in the Heart. In: PLoS One. 2012 ; Vol. 7, No. 12.
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