DOI: 10.1002/ame2.70060
Development of an efficient mice model of cancer-associated cardiac cachexia
Shijie Xiong
Huiting Zheng
Teng Wu
Jing Tan
Tongsheng Huang
Conghui Shen
Yuanjun Ji
Mengying Liu
Junhong Wan
Weibin Cai
Abstract：Background: Cancer-associated cardiac cachexia (CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed.
Methods: This study established CACC models in C57BL/6J and BALB/c mice using orthotopic, intra-abdominal, and hematogenous metastatic tumor induction. Multimodal cardiac assessments, including echocardiography, transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis, and ex vivo cardiomyocyte contractility assays, were systematically applied.
Results: Metastatic burden triggered CACC characterized by cardiac mass reduction, epicardial fat depletion, interstitial fibrosis, and electrocardiographic abnormalities. Histopathological analysis revealed cardiomyocyte atrophy, myofibrillar disarray, mitochondrial dysfunction, and ubiquitin-mediated Myh6 degradation via MuRF-1, accompanied by compensatory Myh7 upregulation. These findings mechanistically link tumor-induced cachexia to cardiac dysfunction through contractile protein remodeling.
Conclusion: This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer-related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration.
Keywords：cachexiacardiac atrophycontractilitymyocardial myosinonco-cardiology
Publication Date：2025-11-30
Online Publishing Date：2026-01-09(First online date of this platform, not the publication date of the document)
Pages：11( 1960-1970 )