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Protective effect of pharmacological castration on metabolic perturbations and cardiovascular disease in the hyperglycemic male ApoE-/-:Ins2+/Akita mouse model.
Duivenvoorden, Wilhelmina C M; Naeim, Magda; Hopmans, Sarah N; Yousef, Sadiya; Werstuck, Geoff H; Dason, Shawn; Pinthus, Jehonathan H.
Afiliação
  • Duivenvoorden WCM; Department of Surgery, Division of Urology, McMaster University, Hamilton, ON, Canada.
  • Naeim M; Research Institute of St. Joe's, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
  • Hopmans SN; Department of Surgery, Division of Urology, McMaster University, Hamilton, ON, Canada.
  • Yousef S; Department of Surgery, Division of Urology, McMaster University, Hamilton, ON, Canada.
  • Werstuck GH; Department of Surgery, Division of Urology, McMaster University, Hamilton, ON, Canada.
  • Dason S; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
  • Pinthus JH; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Prostate Cancer Prostatic Dis ; 24(2): 389-397, 2021 06.
Article em En | MEDLINE | ID: mdl-32989260
BACKGROUND: Unlike in other mouse models of atherogenesis, it has recently been suggested that orchiectomy plays a role in accelerating atherosclerosis and inhibiting the progression of cardiovascular disease in the ApoE-/-:Ins2+/Akita mouse model of hyperglycemia. Androgen-deprivation therapy (ADT) is a common treatment for prostate cancer, a population with high prevalence of cardiovascular disease and its risk factors. Our objectives were to test and further characterize the effects of pharmacological castration which is currently the acceptable modality to deliver ADT in the clinic. METHODS: Male ApoE-/-:Ins2+/Akita mice received one of three modes of ADT (gonadotropin-releasing hormone (GnRH)-antagonist (degarelix), GnRH-agonist (leuprolide), or bilateral orchiectomy) and were compared to corresponding untreated control mice (n = 9-13/group). Mice were followed for 5 months. Body weight, fasting blood glucose, glucose tolerance, serum C-peptide, leptin, and testosterone levels along with atherosclerotic aortic plaque size and characteristics were determined. In a separate experiment, the survival of mice, untreated and on ADT, was determined. RESULTS: Castration was achieved for all three modes of ADT. However, degarelix-treated mice gained significantly less weight, had lower serum leptin levels and systolic blood pressure compared to orchiectomy and leuprolide-treated mice. ADT improved dysglycemia and atherosclerotic burden. GnRH-antagonist significantly improved survival compared to GnRH-agonist but not compared to orchiectomy. CONCLUSIONS: Further characterization of the ApoE-/-:Ins2+/Akita mouse model confirms that pharmacological ADT ameliorated metabolic syndrome and cardiovascular complications. Improved dysglycemia and atherosclerosis associated with increased survival which was longest after degarelix followed by orchiectomy.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Orquiectomia / Doenças Cardiovasculares / Síndrome Metabólica / Modelos Animais de Doenças / Fatores de Proteção / Hiperglicemia / Antagonistas de Androgênios Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Orquiectomia / Doenças Cardiovasculares / Síndrome Metabólica / Modelos Animais de Doenças / Fatores de Proteção / Hiperglicemia / Antagonistas de Androgênios Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article