{Reference Type}: Journal Article
{Title}: Cardiac Atrophy, Dysfunction, and Metabolic Impairments: A Cancer-Induced Cardiomyopathy Phenotype.
{Author}: Ogilvie LM;Delfinis LJ;Coyle-Asbil B;Vudatha V;Alshamali R;Garlisi B;Pereira M;Matuszewska K;Garibotti MC;Gandhi S;Brunt KR;Wood GA;Trevino JG;Perry CGR;Petrik J;Simpson JA;
{Journal}: Am J Pathol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 18
{Factor}: 5.77
{DOI}: 10.1016/j.ajpath.2024.06.008
{Abstract}: 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. Here, the authors used orthotopic, syngeneic models of epithelial ovarian cancer and pancreatic ductal adenocarcinoma, and a patient-derived pancreatic xenograft model, to define the impacts of malignancy on cardiac structure, function, and metabolism. Tumor-bearing mice develop 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, the authors cross-validate with two cancer types, 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.