Breast Cancer Promotes Cardiac Dysfunction Through Deregulation of Cardiomyocyte Ca 2+ ‐Handling Protein Expression That is Not Reversed by Exercise Training

Figures

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  Figure 1. Experimental protocol. ETT indicates exercise tolerance test; PNM, palpable and not measurable tumor; Pre, pre phase tumor growth (BASELINE); and Post, post phase tumor growth (END).

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  Figure 2. Morphological and functional cardiac parameters in mouse mammary tumor virus–polyomavirus middle T antigen (MMTV‐PyMT)− and MMTV‐PyMT+ mice in the pre‐experimental and post‐experimental protocol. Left‐ventricular (LV) end‐diastolic diameter (LVEDD) (A); LV end‐diastolic volume (LVEDV) (B); LV end‐systolic diameter (LVESD) (C); LV end‐systolic volume (LVESV) (D); left atrium (LA) (E); and LV mass (F). Parameters were corrected by weight. LVEDD: P group<0.001, P interaction=0.417; LVEDV: P group=0.003, P interaction=0.437; LA: P interaction=0.004; post hoc test: * P=0.030, between group difference and †† P<0.001, within MMTV‐PyMT+ group difference; and LV mass: P group<0.001, P interaction=0.365. Generalized estimation equations with normal distribution and identity link function using AR(1) correlation matrix between evaluations followed by Bonferroni multiple comparison. Values are expressed as means and SD. Four mice in the MMTV‐PyMT− and 2 mice in the MMTV‐PyMT+ were excluded from this analysis because of poor imaging quality on echocardiography. Thus, 10 mice in the MMTV‐PyMT− and 13 mice in the MMTV‐PyMT+ were involved in this analysis. Of note, 2 LA measures were not…

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  Figure 3. Cardiac function by speckle tracking in mouse mammary tumor virus–polyomavirus middle T antigen (MMTV‐PyMT)− and MMTV‐PyMT+—longitudinal long‐axis strain (A) and strain rate (B). Longitudinal strain (P group<0.001, P interaction=0.126) and strain rate (P group=0.030, P interaction=0.168) were lower in MMTV‐PyMT+ mice when compared with MMTV‐PyMT− mice. Pre: pre phase tumor growth and post: post phase tumor growth. Generalized estimation equations with normal distribution and identity link function using AR(1) correlation matrix between evaluations. Values are expressed as means and SD. Three mice in the MMTV‐PyMT− and 3 mice in the MMTV‐PyMT+ groups were excluded from the speckle‐tracking analysis because of poor imaging quality. Thus, 11 mice in the MMTV‐PyMT− and 12 mice in the MMTV‐PyMT+ were involved in this analysis.

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  Figure 4. Cardiac myocyte Ca2+‐handling proteins in mouse mammary tumor virus–polyomavirus middle T antigen (MMTV‐PyMT)− and MMTV‐PyMT+ mice—phospholamban (A); SERCA2a (sarcoplasmic or endoplasmic reticulum calcium 2 ATPase) (B); phosphorilated phospholamban (p‐phospholamban) (C); sodium/calcium exchanger (NCX) (D); and SERCA2a/phospholambam ratio (E). Western blot bands are shown for each protein. In the MMTV‐PyMT+ mice, phospholamban protein expression was increased (P=0.011) and SERCA2a protein expression was not different between the MMTV‐PyMT+ and MMTV‐PyMT− groups (P=0.165). SERCA2a/phospholamban ratio was reduced in the MMTV‐PyMT+ mice (P=0.007). p‐Phospholamban and NCX protein expression were decreased (P=0.038 and P=0.017, respectively) compared with MMTV‐PyMT− mice. Mann‐Whitney test. Values are expressed as medians and interquartile ranges (IQRs). Animals per group: 7 MMTV‐PyMT− and 7 MMTV‐PyMT+.