Key result
Cancer burden triggers heart failure-like dysfunction, cutting peak left ventricular pressure by ~20%.
Why the study?
Although skeletal muscle wasting in cancer cachexia is extensively characterized, limited studies have investigated how cardiac structure and function are affected by therapy-naive cancer.
Does therapy-naive cancer induce cardiac atrophy, dysfunction, and metabolic impairments in preclinical models?
Does therapy-naive cancer induce cardiac atrophy, dysfunction, and metabolic impairments in preclinical models?
Therapy-naive cancer induces structural, functional, and metabolic cardiomyopathy in preclinical models, highlighting the direct impact of malignancy on cardiac health independent of cardiotoxic 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.
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Ogilvie et al. (2024) studied Cancer-induced cardiomyopathy. Orthotopic tumor induction (ovarian and pancreatic cancer) vs. Sham (saline injection) was evaluated on Maximum left ventricular pressure (LVP Max) in mmHg (p=<0.0001). Tumor-bearing mice developed cardiac atrophy, intrinsic systolic and diastolic dysfunction, arterial hypotension, and a metabolic shift characteristic of heart failure.
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