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Study · Animal study (in vivo) · mouse · 2016

4 results

Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE(-/-) mice.

Knutsson A, Hsiung S, Celik S, Rattik S, Mattisson IY, Wigren M, Scher HI, Nilsson J, Hultgårdh-Nilsson A

Scientific reports18 May 2016Cited by 44 (Europe PMC)

PMID27189011 (opens in a new tab)PMCIDPMC4870555 (opens in a new tab)DOI10.1038/srep26220 (opens in a new tab)PepBankPUB-27189011
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Summary

Androgen-deprivation therapy (ADT) for prostate cancer has been associated with increased risk for development of cardiovascular events and recent pooled analyses of randomized intervention trials suggest that this primarily is the case for patients with pre-existing cardiovascular disease treated with gonadotropin-releasing hormone receptor (GnRH-R) agonists. In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice. A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery. After 4 weeks of ADT, increased areas of necrosis was observed in stable plaques from leuprolide-treated mice (median and IQR plaque necrotic area in control, degarelix and leuprolide-treated mice were 0.6% (IQR 0-3.1), 0.2% (IQR 0-4.4) and 11.0% (IQR 1.0-19.8), respectively). There was also evidence of increased inflammation as assessed by macrophage immunohistochemistry in the plaques from leuprolide-treated mice, but we found no evidence of such changes in plaques from control mice or mice treated with degarelix. Necrosis destabilizes plaques and increases the risk for rupture and development of acute cardiovascular events. Destabilization of pre-existing atherosclerotic plaques could explain the increased cardiovascular risk in prostate cancer patients treated with GnRH-R agonists.
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)Efficacy outcome

    In ApoE(-/-) mice, median stable-plaque necrotic area was 0.2% with degarelix and 0.6% in controls.

    In plain wordsIn mice, median stable-plaque necrotic area was 0.2% with degarelix and 0.6% in controls.

    Peptide
    Degarelix
    Outcome
    DecreaseStable-plaque necrotic area versus control
    Study

    micen: not reported in source

    ApoE(-/-) mice with established carotid atherosclerotic plaques
    Comparator
    Control
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · 4 weeksAs given in this study (mice).

    Measurements

    IQR
    0 to 4.4%
    degarelix
    IQR
    0 to 3.1%
    control

    Source sentences

    Summary
    After 4 weeks of ADT, increased areas of necrosis was observed in stable plaques from leuprolide-treated mice (median and IQR plaque necrotic area in control, degarelix and leuprolide-treated mice were 0.6% (IQR 0-3.1), 0.2% (IQR 0-4.4) and 11.0% (IQR 1.0-19.8), respectively).
    2 context sentences
    Summary · context
    In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice.
    Summary · context
    A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In ApoE(-/-) mice, median stable-plaque necrotic area was 0.2% with degarelix versus 11.0% with leuprolide.

    In plain wordsIn mice, median stable-plaque necrotic area was lower with degarelix than with leuprolide.

    Peptide
    Degarelix
    Outcome
    DecreaseStable-plaque necrotic area versus leuprolide
    Study

    micen: not reported in source

    ApoE(-/-) mice with established carotid atherosclerotic plaques
    Comparator
    Leuprolide
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated · 4 weeksAs given in this study (mice).

    Measurements

    IQR
    0 to 4.4%
    degarelix
    IQR
    1 to 19.8%
    leuprolide

    Source sentences

    Summary
    After 4 weeks of ADT, increased areas of necrosis was observed in stable plaques from leuprolide-treated mice (median and IQR plaque necrotic area in control, degarelix and leuprolide-treated mice were 0.6% (IQR 0-3.1), 0.2% (IQR 0-4.4) and 11.0% (IQR 1.0-19.8), respectively).
    2 context sentences
    Summary · context
    In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice.
    Summary · context
    A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In ApoE(-/-) mice, neither degarelix nor control plaques showed evidence of increased inflammation by macrophage immunohistochemistry.

    In plain wordsIn mice, neither degarelix nor control plaques showed evidence of increased inflammation.

    Peptide
    Degarelix
    Outcome
    No significant changePlaque inflammation versus control
    Study

    micen: not reported in source

    ApoE(-/-) mice with established carotid atherosclerotic plaques
    Comparator
    Control
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated · 4 weeksAs given in this study (mice).

    Source sentences

    Summary
    There was also evidence of increased inflammation as assessed by macrophage immunohistochemistry in the plaques from leuprolide-treated mice, but we found no evidence of such changes in plaques from control mice or mice treated with degarelix.
    2 context sentences
    Summary · context
    In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice.
    Summary · context
    A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In ApoE(-/-) mice, plaque inflammation increased with leuprolide, but no evidence of such changes appeared with degarelix.

    In plain wordsIn mice, plaque inflammation increased with leuprolide, but no evidence of such changes appeared with degarelix.

    Peptide
    Degarelix
    Outcome
    DecreasePlaque inflammation versus leuprolide
    Study

    micen: not reported in source

    ApoE(-/-) mice with established carotid atherosclerotic plaques
    Comparator
    Leuprolide
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated · 4 weeksAs given in this study (mice).

    Source sentences

    Summary
    There was also evidence of increased inflammation as assessed by macrophage immunohistochemistry in the plaques from leuprolide-treated mice, but we found no evidence of such changes in plaques from control mice or mice treated with degarelix.
    2 context sentences
    Summary · context
    In the present study we investigated the effects of the GnRH-R agonist leuprolide and the GnRH-R antagonist degarelix on established atherosclerotic plaques in ApoE(-/-) mice.
    Summary · context
    A shear stress modifier was used to produce both advanced and more stable plaques in the carotid artery.

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 3Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 2

    27 Oct 2026, 16:37 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    27 Oct 2026, 16:34 UTC

    First added · source update from Europe PMC

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