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Study · Animal study (in vivo) · rat · 2026

4 results

Sacubitril/Valsartan Ameliorates Inflammation and Oxidative Stress in Hypertensive Heart Disease by Upregulating CAMKK2 Protein and Modulating the AMPK/AKT/GSK-3β Axis.

Yang YJ, Li JS

The Kaohsiung journal of medical sciences17 Oct 2025Cited by 1 (Europe PMC)

PMID41104684 (opens in a new tab)PMCIDPMC13147946 (opens in a new tab)DOI10.1002/kjm2.70127 (opens in a new tab)PepBankPUB-41104684
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Summary

Sacubitril/valsartan (Sac/Val) has emerged as an effective compound with myocardium-protective functions in experimental and clinical trials for heart failure. This study investigated the function of Sac/Val in hypertensive heart disease (HHD) and explored the underlying mechanism. Spontaneous hypertensive rats (SHRs) were used as an animal model of HHD. Sac/Val administration ameliorated pathological injury, fibrosis, cell apoptosis, inflammatory cytokine production, and oxidative stress in the myocardial tissues of HHD rats. Similar findings were observed in vitro, where Sac/Val treatment reduced inflammation, oxidative stress, and fibrosis-related markers in Ang II-challenged H9C2 cells. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was identified as a target of Sac/Val which was downregulated in HHD models, and CAMKK2 protein levels were restored by Sac/Val treatment. Lentiviral vector-induced CAMKK2 knockdown reduced the phosphorylation levels of AMPKα, AKT, and GSK-3β, thereby negating the treatment effects of Sac/Val. Further treatment with AICAR, an AMPK agonist, significantly reactivated the AMPK/AKT/GSK-3β cascade and alleviated inflammatory injury in both models. Collectively, this study suggests that Sac/Val ameliorates inflammation and oxidative stress in HHD by restoring the CAMKK2 protein and activating the AMPK/AKT/GSK-3β cascade.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Mechanism

    In hypertensive rats, further AICAR treatment reactivated the AMPK/AKT/GSK-3β cascade after CAMKK2 knockdown impaired Sac/Val effects.

    In plain wordsIn rats, additional AICAR restored signaling after gene suppression impaired sacubitril/valsartan effects.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseAMPK/AKT/GSK-3β cascade reactivation
    Study

    ratn: not reported in source

    Spontaneously hypertensive rats with CAMKK2 knockdown
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Further treatment with AICAR, an AMPK agonist, significantly reactivated the AMPK/AKT/GSK-3β cascade and alleviated inflammatory injury in both models.
    2 context sentences
    Summary · context
    Lentiviral vector-induced CAMKK2 knockdown reduced the phosphorylation levels of AMPKα, AKT, and GSK-3β, thereby negating the treatment effects of Sac/Val.
    Summary · context
    Spontaneous hypertensive rats (SHRs) were used as an animal model of HHD.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In hypertensive rats, further AICAR treatment alleviated inflammatory injury after CAMKK2 knockdown impaired Sac/Val effects.

    In plain wordsIn rats, additional AICAR reduced inflammatory injury after gene suppression impaired sacubitril/valsartan effects.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseInflammatory injury
    Study

    ratn: not reported in source

    Spontaneously hypertensive rats with CAMKK2 knockdown
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Further treatment with AICAR, an AMPK agonist, significantly reactivated the AMPK/AKT/GSK-3β cascade and alleviated inflammatory injury in both models.
    2 context sentences
    Summary · context
    Lentiviral vector-induced CAMKK2 knockdown reduced the phosphorylation levels of AMPKα, AKT, and GSK-3β, thereby negating the treatment effects of Sac/Val.
    Summary · context
    Spontaneous hypertensive rats (SHRs) were used as an animal model of HHD.
  3. 03LabIn vitro (cells)Mechanism

    In Ang II-challenged H9C2 cells, further AICAR treatment reactivated the AMPK/AKT/GSK-3β cascade after CAMKK2 knockdown impaired Sac/Val effects.

    In plain wordsIn cells, additional AICAR restored signaling after gene suppression impaired sacubitril/valsartan effects.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseAMPK/AKT/GSK-3β cascade reactivation
    Study

    n: not reported in source

    Ang II-challenged H9C2 cells with CAMKK2 knockdown
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Further treatment with AICAR, an AMPK agonist, significantly reactivated the AMPK/AKT/GSK-3β cascade and alleviated inflammatory injury in both models.
    2 context sentences
    Summary · context
    Lentiviral vector-induced CAMKK2 knockdown reduced the phosphorylation levels of AMPKα, AKT, and GSK-3β, thereby negating the treatment effects of Sac/Val.
    Summary · context
    Similar findings were observed in vitro, where Sac/Val treatment reduced inflammation, oxidative stress, and fibrosis-related markers in Ang II-challenged H9C2 cells.
  4. 04LabIn vitro (cells)Mechanism

    In Ang II-challenged H9C2 cells, further AICAR treatment alleviated inflammatory injury after CAMKK2 knockdown impaired Sac/Val effects.

    In plain wordsIn cells, additional AICAR reduced inflammatory injury after gene suppression impaired sacubitril/valsartan effects.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseInflammatory injury
    Study

    n: not reported in source

    Ang II-challenged H9C2 cells with CAMKK2 knockdown
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Further treatment with AICAR, an AMPK agonist, significantly reactivated the AMPK/AKT/GSK-3β cascade and alleviated inflammatory injury in both models.
    2 context sentences
    Summary · context
    Lentiviral vector-induced CAMKK2 knockdown reduced the phosphorylation levels of AMPKα, AKT, and GSK-3β, thereby negating the treatment effects of Sac/Val.
    Summary · context
    Similar findings were observed in vitro, where Sac/Val treatment reduced inflammation, oxidative stress, and fibrosis-related markers in Ang II-challenged H9C2 cells.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 12:50 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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