Academic Journal
C-Type Natriuretic Peptide Preserves Vascular and Cardiac Function in Sepsis.
| Τίτλος: | C-Type Natriuretic Peptide Preserves Vascular and Cardiac Function in Sepsis. |
|---|---|
| Συγγραφείς: | Moyes AJ; Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts & The London Hospitals, Queen Mary University of London, United Kingdom (A.J.M., C.S., L.Y., C.P.-T., A.T.S., R.S.B., S.M., A.A.A., A.J.H.)., Sand C; Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts & The London Hospitals, Queen Mary University of London, United Kingdom (A.J.M., C.S., L.Y., C.P.-T., A.T.S., R.S.B., S.M., A.A.A., A.J.H.)., Young L; Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts & The London Hospitals, Queen Mary University of London, United Kingdom (A.J.M., C.S., L.Y., C.P.-T., A.T.S., R.S.B., S.M., A.A.A., A.J.H.)., Pérez-Ternero C; Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts & The London Hospitals, Queen Mary University of London, United Kingdom (A.J.M., C.S., L.Y., C.P.-T., A.T.S., R.S.B., S.M., A.A.A., A.J.H.)., Salam AT; Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts & The London Hospitals, Queen Mary University of London, United Kingdom (A.J.M., C.S., L.Y., C.P.-T., A.T.S., R.S.B., S.M., A.A.A., A.J.H.)., Baliga RS; Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts & The London Hospitals, Queen Mary University of London, United Kingdom (A.J.M., C.S., L.Y., C.P.-T., A.T.S., R.S.B., S.M., A.A.A., A.J.H.)., Mohammad S; Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts & The London Hospitals, Queen Mary University of London, United Kingdom (A.J.M., C.S., L.Y., C.P.-T., A.T.S., R.S.B., S.M., A.A.A., A.J.H.)., Antcliffe DB; Faculty of Medicine, Division of Anesthetics, Pain Medicine and Intensive Care, Imperial College London, United Kingdom (D.B.A., A.C.G.)., Gordon AC; Faculty of Medicine, Division of Anesthetics, Pain Medicine and Intensive Care, Imperial College London, United Kingdom (D.B.A., A.C.G.)., Aubdool AA; Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts & The London Hospitals, Queen Mary University of London, United Kingdom (A.J.M., C.S., L.Y., C.P.-T., A.T.S., R.S.B., S.M., A.A.A., A.J.H.)., Hobbs AJ; Faculty of Medicine and Dentistry, William Harvey Research Institute, Barts & The London Hospitals, Queen Mary University of London, United Kingdom (A.J.M., C.S., L.Y., C.P.-T., A.T.S., R.S.B., S.M., A.A.A., A.J.H.). |
| Πηγή: | Hypertension (Dallas, Tex. : 1979) [Hypertension] 2026 Jun; Vol. 83 (6), pp. e25938. Date of Electronic Publication: 2026 Feb 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Lippincott, Williams & Wilkins Country of Publication: United States NLM ID: 7906255 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4563 (Electronic) Linking ISSN: 0194911X NLM ISO Abbreviation: Hypertension Subsets: MEDLINE |
| Imprint Name(s): | Publication: Original Publication: [Dallas, Tex.] : [American Heart Association], [©1979]- |
| Ιατρικοί όροι (MeSH): | Natriuretic Peptide, C-Type*/pharmacology , Natriuretic Peptide, C-Type*/blood , Sepsis*/physiopathology , Sepsis*/drug therapy , Sepsis*/blood , Sepsis*/metabolism , Endothelium, Vascular*/drug effects , Endothelium, Vascular*/physiopathology , Endothelium, Vascular*/metabolism, Hemodynamics/drug effects ; Hemodynamics/physiology ; Biomarkers/blood ; Animals ; Mice ; Mice, Knockout ; Disease Models, Animal ; Humans ; Male ; Mice, Inbred C57BL |
| Περίληψη: | Background: Sepsis is a life-threatening condition and a major cause of mortality in intensive care units worldwide, a clear unmet medical need. CNP (C-type natriuretic peptide) regulates inflammation and cardiovascular homeostasis, but its involvement in sepsis pathogenesis is not fully elucidated. This study investigated the intrinsic role of CNP, and therapeutic potential of the peptide, in offsetting the pathogenesis of sepsis. Methods: Plasma concentrations of CNP, and its N-terminal cleavage product NT-proCNP (N-terminal pro-CNP), were measured in sepsis patients. Cardiac function, vascular hemodynamics, endothelial integrity, and biomarkers of inflammation were analyzed in wild-type, endothelium-restricted (ecCNP-/-), or cardiomyocyte-restricted (cmCNP-/-) CNP knockout animals, or global NPR (natriuretic peptide receptor)-C-/- deficient mice, in etiologically distinct models of sepsis. CNP (0.2 mg/kg per d) was infused to rescue any adverse phenotype and probe therapeutic potential. Results: Circulating [NT-proCNP] increased in sepsis patients and was associated with reduced disease severity. ecCNP-/- mice exhibited an aggravated phenotype compared with wild-type mice in experimental sepsis, exemplified by impaired microcirculatory flow, edema, and increased expression of inflammatory biomarkers. In addition, cmCNP-/- animals showed overt cardiac dysfunction following lipopolysaccharide treatment. This worsened phenotype was mirrored in NPR-C-/- mice, implying that this cognate NPR subtype underpins the salutary actions of endogenous CNP. Pharmacological CNP administration improved microvascular perfusion, cardiac output, and inflammation in wild-type and ecCNP-/-, but not NPR-C-/-, mice. Conclusions: Endogenous CNP plays a protective role in sepsis by preserving microvascular perfusion, reducing inflammation, maintaining endothelial integrity, and sustaining cardiac function via NPR-C. Pharmacologically targeting CNP signaling warrants further evaluation as a potential therapeutic opportunity in sepsis. |
| Competing Interests: | A.J. Hobbs is a scientific advisory board member/consultant for PharmaIN Corporation, Bionevix Ltd, and Novo Nordisk. A.C. Gordon received consulting fees from AstraZeneca, Beckman Coulter, and VVB Bio, and speaker fees from Fresenius Kabi. The other authors report no conflicts. |
| Contributed Indexing: | Keywords: arterial pressure; hypotension; lipopolysaccharides; natriuretic peptide, C-type; sepsis |
| Substance Nomenclature: | 127869-51-6 (Natriuretic Peptide, C-Type) 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260204 Date Completed: 20260707 Latest Revision: 20260707 |
| Update Code: | 20260707 |
| PubMed Central ID: | PMC13189390 |
| DOI: | 10.1161/HYPERTENSIONAHA.125.25938 |
| PMID: | 41636071 |
| Βάση Δεδομένων: | MEDLINE |
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