Evidence for cardiac atrophic remodeling in cancer-induced cachexia in mice
Open Access
- 5 August 2011
- journal article
- research article
- Published by Spandidos Publications in International Journal of Oncology
- Vol. 39 (5), 1321-1326
- https://doi.org/10.3892/ijo.2011.1150
Abstract
Cachexia is a common complication in cancer patients, which dramatically reduces quality of life and survival. In contrast to the well-studied feature of skeletal muscle loss, alterations in cardiac muscle are unclear. Recently, we reported that heart contractile function was significantly impaired in mice with colon-26 (C26) tumors, a widely used rodent model of cancer cachexia. In the present study, we investigated the potential underlying mechanisms for decreased heart function, specifically related to cardiac remodeling and atrophy. In cachectic mice bearing C26 tumors compared to mice without tumors, there was a gene expression pattern for cardiac remodeling, including increased BNP and c-fos, decreased PPAR alpha and its responsive gene CPT1 beta, and a switch from 'adult' isoforms (MHC alpha, GLUT4) to 'fetal' isoforms (MHC beta and GLUT1). Echocardiography identified a decreased cardiac wall thickness. RT-PCR and Western blotting revealed a decreased amount of cardiac myolibrillar proteins MHC and troponin I, induced expression of E-3 ligases (MuRF-1 and Atrogin-1) and increased protein ubiquitination, providing evidence for cardiac atrophy in mice with cancer cachexia. Regulatory signaling pathways mediating these changes may include p44/42 MAPK. Together, these data provide evidence that pathways leading to cardiac remodeling and atrophy occur in mice with C26 cachexia.Keywords
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