Journal
JOURNAL OF THE AMERICAN HEART ASSOCIATION
Volume 10, Issue 5, Pages -Publisher
WILEY
DOI: 10.1161/JAHA.120.018076
Keywords
breast cancer; Ca2+ handling; cardiac function
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2015/22814-5]
- FAPESP [2014/13690-8, 15/19076-2]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [306261/2016-2, 313479/2017-8, 307227/2018-9, 303573/2015-5]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [15/19076-2] Funding Source: FAPESP
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Breast cancer patients have alterations in cardiac function and cardiomyocyte Ca2+-handling protein expression, leading to decreased exercise capacity and subclinical left ventricular dysfunction. Exercise training does not prevent or reverse these changes.
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 cm(3). 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.
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