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Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca²⁺-Handling Protein Expression That is Not Reversed by Exercise Training.

ABSTRACT: 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- (P_interaction=0.031). Longitudinal strain (P_group <0.001) and strain rate (P_group=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 (P_group=0.038) and end-diastolic volume (P_group=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.

SUBMITTER: da Costa TSR

PROVIDER: S-EPMC8174298 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca<sup>2+</sup>-Handling Protein Expression That is Not Reversed by Exercise Training.

da Costa Tassia S R TSR Urias Ursula U Negrao Marcelo V MV Jordão Camila P CP Passos Clévia S CS Gomes-Santos Igor L IL Salemi Vera Maria C VMC Camargo Anamaria A AA Brum Patricia C PC Oliveira Edilamar M EM Hajjar Ludhmila A LA Chammas Roger R Filho Roberto K RK Negrao Carlos E CE

Journal of the American Heart Association 20210223 5

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 Ca<sup>2+</sup>-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 w ...[more]

PMID: 33619982

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Dataset Information

Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca²⁺-Handling Protein Expression That is Not Reversed by Exercise Training.

Publications

Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca<sup>2+</sup>-Handling Protein Expression That is Not Reversed by Exercise Training.

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Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca2+-Handling Protein Expression That is Not Reversed by Exercise Training.

Publications

Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca<sup>2+</sup>-Handling Protein Expression That is Not Reversed by Exercise Training.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca²⁺-Handling Protein Expression That is Not Reversed by Exercise Training.