Myocardial dysfunction in an animal model of cancer cachexia

LIFE SCIENCES

卷:88

Article

Xu, Hui²  Crawford, Danielle²  Hutchinson, Kirk R.³  Lucchesi, Pamela A.⁴  McCarthy, Donna O.²  Wold, Loren E.^1,4,5 

[1] Ohio State Univ, Ctr Cardiovasc & Pulm Res, Nationwide Childrens Hosp, Res Inst,Dept Pediat Physiol & Cell Biol, Columbus, OH 43205 USA

[2] Ohio State Univ, Coll Nursing, Columbus, OH 43205 USA

[3] Louisiana State Univ, Dept Pharmacol & Expt Therapeut, Hlth Sci Ctr, New Orleans, LA USA

[4] Ohio State Univ, Dept Pediat, Columbus, OH 43205 USA

[5] Ohio State Univ, Dept Physiol & Cell Biol, Columbus, OH 43205 USA

关键词: Cancer;    Cachexia;    Myocardial function;    Cardiomyocyte;    Autophagy;    Ubiquitin;   

DOI  :  10.1016/j.lfs.2010.12.010

来源: Elsevier

【 摘 要 】

Aims: Fatigue is a common occurrence in cancer patients regardless of tumor type or anti-tumor therapies and is an especially problematic symptom in persons with incurable tumor disease. In rodents, tumor-induced fatigue is associated with a progressive loss of skeletal muscle mass and increased expression of biomarkers of muscle protein degradation. The purpose of the present study was to determine if muscle wasting and expression of biomarkers of muscle protein degradation occur in the hearts of tumor-bearing mice, and if these effects of tumor growth are associated with changes in cardiac function. Main methods: The colon26 adenocarcinoma cell line was implanted into female CD2F1 mice and skeletal muscle wasting, in vivo heart function, in vitro cardiomyocyte function, and biomarkers of muscle protein degradation were determined. Key findings: Expression of biomarkers of protein degradation were increased in both the gastrocnemius and heart muscle of tumor-bearing mice and caused systolic dysfunction in vivo. Cardiomyocyte function was significantly depressed during both cellular contraction and relaxation. Significance: These results suggest that heart muscle is directly affected by tumor growth, with myocardial function more severely compromised at the cellular level than what is observed using echocardiography. (C) 2010 Elsevier Inc. All rights reserved.

【 授权许可】

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