Sacubitril/Valsartan inhibits M1 type macrophages polarization in acute myocarditis by targeting C-type natriuretic peptide.

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  • Additional Information
    • Source:
      Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE
    • Publication Information:
      Publication: Paris : Editions Scientifiques Elsevier
      Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-
    • Subject Terms:
      Myocarditis*/drug therapy ; Myocarditis*/metabolism ; Myocarditis*/pathology ; Macrophages*/drug effects ; Macrophages*/metabolism ; Aminobutyrates*/pharmacology ; Valsartan*/pharmacology ; Biphenyl Compounds*/pharmacology ; Natriuretic Peptide, C-Type*/pharmacology ; Drug Combinations*; Animals ; Mice ; RAW 264.7 Cells ; Male ; Humans ; Tetrazoles/pharmacology ; Acute Disease ; Disease Models, Animal ; Female ; Cytokines/metabolism ; Cytokines/blood ; Mice, Inbred C57BL ; Anti-Inflammatory Agents/pharmacology ; Cell Polarity/drug effects
    • Abstract:
      Studies have shown that Sacubitril/valsartan (Sac/Val) can reduce myocardial inflammation in myocarditis mice, in addition to its the recommended treatment of heart failure. However, the underlying mechanisms of Sac/Val in myocarditis remain unclear. C-type natriuretic peptide (CNP), one of the targeting natriuretic peptides of Sac/Val, was recently reported to exert cardio-protective and anti-inflammatory effects in cardiovascular systems. Here, we focused on circulating levels of CNP in patients with acute myocarditis (AMC) and whether Sac/Val modulates inflammation by targeting CNP in experimental autoimmune myocarditis (EAM) mice as well as LPS-induced RAW 264.7 cells and bone marrow derived macrophages (BMDMs) models. Circulating CNP levels were higher in AMC patients compared to healthy controls, and these levels positively correlated with the elevated inflammatory cytokines IL-6 and monocyte count. In EAM mice, Sac/Val alleviated myocardial inflammation while augmenting circulating CNP levels rather than BNP and ANP, accompanied by reduction in intracardial M1 macrophage infiltration and expression of inflammatory cytokines IL-1β, TNF-α, and IL-6. Furthermore, Sac/Val inhibited CNP degradation and directly blunted M1 macrophage polarization in LPS-induced RAW 264.7 cells and BMDMs. Mechanistically, the effects might be mediated by the NPR-C/cAMP/JNK/c-Jun signaling pathway apart from NPR-B/cGMP/NF-κB pathway. In conclusion, Sac/Val exerts a protective effect in myocarditis by increasing CNP concentration and inhibiting M1 macrophages polarization.
      Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
    • Contributed Indexing:
      Keywords: CNP; JNK/c-Jun; NPR-C; Sacubitril/valsartan; macrophages; myocarditis
    • Accession Number:
      0 (Aminobutyrates)
      80M03YXJ7I (Valsartan)
      WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination)
      0 (Biphenyl Compounds)
      127869-51-6 (Natriuretic Peptide, C-Type)
      0 (Drug Combinations)
      0 (Tetrazoles)
      0 (Cytokines)
      0 (Anti-Inflammatory Agents)
    • Publication Date:
      Date Created: 20240406 Date Completed: 20240430 Latest Revision: 20240502
    • Publication Date:
      20240502
    • Accession Number:
      10.1016/j.biopha.2024.116535
    • Accession Number:
      38581923