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
Guangdong Engineering & Technology Research Center for Disease-Model Animals,Laboratory Animal Center,Sun Yat-Sen University,Guangzhou,Guangdong,China;Department of Biochemistry,Zhongshan School of Medicine,Sun Yat-Sen University,Guangzhou,Guangdong,China
摘要：Background:Cancer-associated cardiac cachexia(CACC)refers to cardiac injury in cancer patients in a malignant state,but preclinical animal models remain inad-equately 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 car-diomyocyte 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 mechanisti-cally 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 ap-proach delineates a hierarchical progression from subcellular dysfunction to macro-scopic cardiac deterioration.
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论文发表日期：2025-11-30
在线出版日期：2026-01-09（本平台首次上网日期，不代表文献的发表时间）
页数：11( 1960-1970 )
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