The NO Pathway as a Target in Patients with Stable and Advanced Heart Failure: An Additional Arrow in Our Quiver!

D'Elia, S; Gentile, C; Solimene, A; Franzese, R; Luisi, E; Caiazzo, A; Marotta, L; Covino, S; Natale, F; Loffredo, FS; Golino, P; Cimmino, G

The NO Pathway as a Target in Patients with Stable and Advanced Heart Failure: An Additional Arrow in Our Quiver!

D'Elia, S Gentile, C

Solimene, A Franzese, R Luisi, E Caiazzo, A Marotta, L Covino, S Natale, F Loffredo, FS Golino, P Cimmino, G

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Biomolecules, 2025, 15, (10), pp. 1420
Issue Date:: 2025-10-06

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Field	Value	Language
dc.contributor.author	D'Elia, S
dc.contributor.author	Gentile, C https://orcid.org/0000-0002-3689-4275
dc.contributor.author	Solimene, A
dc.contributor.author	Franzese, R
dc.contributor.author	Luisi, E
dc.contributor.author	Caiazzo, A
dc.contributor.author	Marotta, L
dc.contributor.author	Covino, S
dc.contributor.author	Natale, F
dc.contributor.author	Loffredo, FS
dc.contributor.author	Golino, P
dc.contributor.author	Cimmino, G
dc.date.accessioned	2026-02-03T09:06:48Z
dc.date.available	2025-10-03
dc.date.available	2026-02-03T09:06:48Z
dc.date.issued	2025-10-06
dc.identifier.citation	Biomolecules, 2025, 15, (10), pp. 1420
dc.identifier.issn	2218-273X
dc.identifier.issn	2218-273X
dc.identifier.uri	http://hdl.handle.net/10453/192871
dc.description.abstract	The nitric oxide (NO) pathway is a fundamental regulator of vascular tone, myocardial function, and inflammation. In heart failure (HF), especially in advanced stages, dysregulation of NO-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling contributes to endothelial dysfunction, increased vascular resistance, myocardial fibrosis, and impaired cardiac performance. Chronic inflammation further reduces NO bioavailability, exacerbating HF progression This review synthesizes current knowledge on the role of the NO pathway in HF pathophysiology, with a focus on stable and advanced HF. Special attention is given to patient subgroups with comorbidities such as chronic kidney disease, where modulation of NO signaling may be particularly beneficial. We also evaluate therapeutic strategies targeting NO bioavailability and sGC stimulation. Evidence shows that impaired NO signaling promotes systemic and pulmonary vasoconstriction, elevates ventricular afterload, and worsens cardiac remodeling. Pharmacological agents that restore NO levels or activate downstream effectors such as sGC improve vasodilation, reduce fibrosis, and enhance myocardial relaxation. These effects are especially relevant in advanced HF patients and those with renal impairment, who often exhibit limited responses to conventional therapies. The NO pathway represents a promising therapeutic target in both stable and advanced HF. Modulating this pathway could improve outcomes, particularly in complex populations with multiple comorbidities, highlighting the need for further clinical research and tailored treatments.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation.ispartof	Biomolecules
dc.relation.isbasedon	10.3390/biom15101420
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology
dc.subject.classification	3101 Biochemistry and cell biology
dc.subject.classification	3102 Bioinformatics and computational biology
dc.subject.classification	3206 Medical biotechnology
dc.subject.mesh	Humans
dc.subject.mesh	Heart Failure
dc.subject.mesh	Nitric Oxide
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Animals
dc.subject.mesh	Soluble Guanylyl Cyclase
dc.subject.mesh	Cyclic GMP
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Nitric Oxide
dc.subject.mesh	Cyclic GMP
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Heart Failure
dc.subject.mesh	Soluble Guanylyl Cyclase
dc.subject.mesh	Humans
dc.subject.mesh	Heart Failure
dc.subject.mesh	Nitric Oxide
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Animals
dc.subject.mesh	Soluble Guanylyl Cyclase
dc.subject.mesh	Cyclic GMP
dc.title	The NO Pathway as a Target in Patients with Stable and Advanced Heart Failure: An Additional Arrow in Our Quiver!
dc.type	Journal Article
utslib.citation.volume	15
utslib.location.activity	Switzerland
utslib.for	0601 Biochemistry and Cell Biology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Health Technologies (CHT)
pubs.organisational-group	University of Technology Sydney/UTS Groups/UTS LGBTIQA+ Research Network
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2026-02-03T09:06:46Z
pubs.issue	10
pubs.publication-status	Published online
pubs.volume	15
utslib.citation.issue	10

Abstract:

The nitric oxide (NO) pathway is a fundamental regulator of vascular tone, myocardial function, and inflammation. In heart failure (HF), especially in advanced stages, dysregulation of NO-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling contributes to endothelial dysfunction, increased vascular resistance, myocardial fibrosis, and impaired cardiac performance. Chronic inflammation further reduces NO bioavailability, exacerbating HF progression This review synthesizes current knowledge on the role of the NO pathway in HF pathophysiology, with a focus on stable and advanced HF. Special attention is given to patient subgroups with comorbidities such as chronic kidney disease, where modulation of NO signaling may be particularly beneficial. We also evaluate therapeutic strategies targeting NO bioavailability and sGC stimulation. Evidence shows that impaired NO signaling promotes systemic and pulmonary vasoconstriction, elevates ventricular afterload, and worsens cardiac remodeling. Pharmacological agents that restore NO levels or activate downstream effectors such as sGC improve vasodilation, reduce fibrosis, and enhance myocardial relaxation. These effects are especially relevant in advanced HF patients and those with renal impairment, who often exhibit limited responses to conventional therapies. The NO pathway represents a promising therapeutic target in both stable and advanced HF. Modulating this pathway could improve outcomes, particularly in complex populations with multiple comorbidities, highlighting the need for further clinical research and tailored treatments.

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http://hdl.handle.net/10453/192871