Cardiac alterations in cancer-induced cachexia in mice

Min Tian, Yoshinori Nishijima, Michelle L Asp, Michael B. Stout, Peter J. Reiser, Martha A. Belury

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73 Scopus citations

Abstract

Cachexia is a common syndrome in advanced cancer patients and causes up to 22% of cancer-related deaths. It remains elusive whether cancer cachexia causes heart failure. We investigated the effect of cancer cachexia on heart function and cardiac muscle structure in a mouse model. Male CD2F1 mice were inoculated with either colon-26 adenocarcinoma cells (Tumor group) or vehicle (PBS) (No Tumor group and Pair-fed group). Heart function as measured by fractional shortening in vivo using transthoracic echocardiography was performed on day 14 after tumor or PBS inoculation. At necropsy (day 17), hearts were collected for histology, transmission electron microscopy, RT-PCR and SDS-PAGE analysis. Mice from the Tumor group displayed a significantly reduced fractional shortening compared to mice in the No Tumor and Pair-fed groups. In hearts of the Tumor mice compared to the other groups, there was marked fibrosis and transmission electron microscopy revealed disrupted myocardial ultrastructure. Gene expression of troponin I, a regulator of cardiac muscle contraction, was reduced. Moreover, both mRNA and protein levels of myosin heavy chain (MHC) were altered whereby MHCα (adult isoform) was decreased and MHCβ (fetal isoform) was increased indicating reactivation of the fetal gene expression pattern. In conclusion, heart function was diminished in mice with tumor-induced cachexia, and this impaired function was associated with increased fibrosis, disrupted myocardial structure and altered composition of contractile proteins of cardiac muscle.

Original languageEnglish (US)
Pages (from-to)347-353
Number of pages7
JournalInternational Journal of Oncology
Volume37
Issue number2
DOIs
StatePublished - Aug 1 2010

Keywords

  • Echocardiography
  • Myocardium structure
  • Myosin heavy chain

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    Tian, M., Nishijima, Y., Asp, M. L., Stout, M. B., Reiser, P. J., & Belury, M. A. (2010). Cardiac alterations in cancer-induced cachexia in mice. International Journal of Oncology, 37(2), 347-353. https://doi.org/10.3892/ijo-0000683