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Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca2+-Handling Protein Expression That is Not Reversed by Exercise Training.
da Costa, Tassia S R; Urias, Ursula; Negrao, Marcelo V; Jordão, Camila P; Passos, Clévia S; Gomes-Santos, Igor L; Salemi, Vera Maria C; Camargo, Anamaria A; Brum, Patricia C; Oliveira, Edilamar M; Hajjar, Ludhmila A; Chammas, Roger; Filho, Roberto K; Negrao, Carlos E.
Afiliação
  • da Costa TSR; Heart Institute (InCor) do Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo Brasil.
  • Urias U; Cancer Institute of the State of São Paulo Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo Brasil.
  • Negrao MV; Heart Institute (InCor) do Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo Brasil.
  • Jordão CP; School of Physical Education and Sport Universidade de São Paulo Brasil.
  • Passos CS; Department of Thoracic/Head and Neck Medical Oncology The University of TexasMD Anderson Cancer Center Houston TX.
  • Gomes-Santos IL; Heart Institute (InCor) do Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo Brasil.
  • Salemi VMC; Heart Institute (InCor) do Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo Brasil.
  • Camargo AA; Heart Institute (InCor) do Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo Brasil.
  • Brum PC; Edwin L. Steele Laboratories for Tumor Biology Department of Radiation Oncology, Massachusetts General Hospital & Harvard Medical School Boston MA.
  • Oliveira EM; Heart Institute (InCor) do Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo Brasil.
  • Hajjar LA; Centro de Oncologia Molecular Hospital Sírio-Libanês São Paulo Brazil.
  • Chammas R; School of Physical Education and Sport Universidade de São Paulo Brasil.
  • Filho RK; School of Physical Education and Sport Universidade de São Paulo Brasil.
  • Negrao CE; Heart Institute (InCor) do Hospital das Clínicas Faculdade de Medicina Universidade de São Paulo Brasil.
J Am Heart Assoc ; 10(5): e018076, 2021 02.
Article em En | MEDLINE | ID: mdl-33619982
Background Patients treated for breast cancer have a high incidence of cardiovascular complications. In this study, we evaluated the impact of breast cancer on cardiac function and cardiomyocyte Ca2+-handling protein expression. We also investigated whether exercise training (ET) would prevent these potential alterations. Methods and Results Transgenic mice with spontaneous breast cancer (mouse mammary tumor virus-polyomavirus middle T antigen [MMTV-PyMT+], n=15) and littermate mice with no cancer (MMTV-PyMT-, n=14) were studied. For the ET analysis, MMTV-PyMT+ were divided into sedentary (n=10) and exercise-trained (n=12) groups. Cardiac function was evaluated by echocardiography with speckle-tracking imaging. Exercise tolerance test was conducted on a treadmill. Both studies were performed when the tumor became palpable and when it reached 1 cm3. After euthanasia, Ca2+-handling protein expression (Western blot) was evaluated. Exercise capacity was reduced in MMTV-PyMT+ compared with MMTV-PyMT- (Pinteraction=0.031). Longitudinal strain (Pgroup <0.001) and strain rate (Pgroup=0.030) were impaired. Cardiomyocyte phospholamban was increased (P=0.011), whereas phospho-phospholamban and sodium/calcium exchanger were decreased (P=0.038 and P=0.017, respectively) in MMTV-PyMT+. No significant difference in sarcoplasmic or endoplasmic reticulum calcium 2 ATPase (SERCA2a) was found. SERCA2a/phospholamban ratio was reduced (P=0.007). ET was not associated with increased exercise capacity. ET decreased left ventricular end-systolic diameter (Pgroup=0.038) and end-diastolic volume (Pgroup=0.026). Other morphological and functional cardiac parameters were not improved by ET in MMTV-PyMT+. ET did not improve cardiomyocyte Ca2+-handling protein expression. Conclusions Breast cancer is associated with decreased exercise capacity and subclinical left ventricular dysfunction in MMTV-PyMT+, which is at least partly associated with dysregulation of cardiomyocyte Ca2+ handling. ET did not prevent or reverse these changes.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Condicionamento Físico Animal / Neoplasias da Mama / Doenças Cardiovasculares / Cálcio / Função Ventricular Esquerda / Miócitos Cardíacos / Ventrículos do Coração Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: J Am Heart Assoc Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Condicionamento Físico Animal / Neoplasias da Mama / Doenças Cardiovasculares / Cálcio / Função Ventricular Esquerda / Miócitos Cardíacos / Ventrículos do Coração Tipo de estudo: Diagnostic_studies Limite: Animals Idioma: En Revista: J Am Heart Assoc Ano de publicação: 2021 Tipo de documento: Article