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Cardiac Atrophy, Dysfunction, and Metabolic Impairments: A Cancer-Induced Cardiomyopathy Phenotype.
Ogilvie, Leslie M; Delfinis, Luca J; Coyle-Asbil, Bridget; Vudatha, Vignesh; Alshamali, Razan; Garlisi, Bianca; Pereira, Madison; Matuszewska, Kathy; Garibotti, Madison C; Gandhi, Shivam; Brunt, Keith R; Wood, Geoffrey A; Trevino, Jose G; Perry, Christopher G R; Petrik, Jim; Simpson, Jeremy A.
Afiliação
  • Ogilvie LM; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
  • Delfinis LJ; School of Kinesiology & Health Science and the Muscle Health Research Centre, York University, Toronto, Ontario, Canada.
  • Coyle-Asbil B; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
  • Vudatha V; Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
  • Alshamali R; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
  • Garlisi B; Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
  • Pereira M; Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
  • Matuszewska K; Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
  • Garibotti MC; School of Kinesiology & Health Science and the Muscle Health Research Centre, York University, Toronto, Ontario, Canada.
  • Gandhi S; School of Kinesiology & Health Science and the Muscle Health Research Centre, York University, Toronto, Ontario, Canada.
  • Brunt KR; Department of Pharmacology, Dalhousie Medicine New Brunswick, Saint John, New Brunswick, Canada; IMPART Investigator Team, Saint John, New Brunswick, Canada.
  • Wood GA; Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
  • Trevino JG; Department of Surgery, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
  • Perry CGR; School of Kinesiology & Health Science and the Muscle Health Research Centre, York University, Toronto, Ontario, Canada.
  • Petrik J; Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
  • Simpson JA; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada; IMPART Investigator Team, Saint John, New Brunswick, Canada. Electronic address: jeremys@uoguelph.ca.
Am J Pathol ; 194(10): 1823-1843, 2024 Oct.
Article em En | MEDLINE | ID: mdl-39032600
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. 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Cardiomiopatias Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenótipo / Cardiomiopatias Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article