Tumor-bearing mice with ovarian or pancreatic cancer developed cardiac atrophy, intrinsic systolic and diastolic dysfunction, and metabolic substrate shifts characteristic of heart failure.
Does therapy-naive cancer cause cardiac atrophy, dysfunction, and metabolic impairments in preclinical mouse models?
Therapy-naive cancer directly induces structural, functional, and metabolic cardiomyopathy in preclinical models, independent of cardiotoxic cancer therapies.
Muscle atrophy and weakness are prevalent features of cancer. Although extensive research has characterized skeletal muscle wasting in cancer cachexia, limited studies have investigated how cardiac structure and function are affected by therapy-naive cancer. Herein, orthotopic, syngeneic models of epithelial ovarian cancer and pancreatic ductal adenocarcinoma, and a patient-derived pancreatic xenograft model, were used to define the impact of malignancy on cardiac structure, function, and metabolism. Tumor-bearing mice developed cardiac atrophy and intrinsic systolic and diastolic dysfunction, with arterial hypotension and exercise intolerance. In hearts of ovarian tumor-bearing mice, fatty acid-supported mitochondrial respiration decreased, and carbohydrate-supported respiration increased-showcasing a substrate shift in cardiac metabolism that is characteristic of heart failure. Epithelial ovarian cancer decreased cytoskeletal and cardioprotective gene expression, which was paralleled by down-regulation of transcription factors that regulate cardiomyocyte size and function. Patient-derived pancreatic xenograft tumor-bearing mice show altered myosin heavy chain isoform expression-also a molecular phenotype of heart failure. Markers of autophagy and ubiquitin-proteasome system were upregulated by cancer, providing evidence of catabolic signaling that promotes cardiac wasting. Together, two cancer types were used to cross-validate evidence of the structural, functional, and metabolic cancer-induced cardiomyopathy, thus providing translational evidence that could impact future medical management strategies for improved cancer recovery in patients.
Ogilvie et al. (Thu,) conducted a other in Cancer-induced cardiomyopathy. Tumor-bearing state (ovarian and pancreatic cancer models) was evaluated on Impact of malignancy on cardiac structure, function, and metabolism. Tumor-bearing mice with ovarian or pancreatic cancer developed cardiac atrophy, intrinsic systolic and diastolic dysfunction, and metabolic substrate shifts characteristic of heart failure.