Cardiac Dysfunction in the Mouse Model of Cancer Cachexia and Therapeutic Effects of Voluntary Exercise

<p>【Aims】Recently, the interdisciplinary field of cardio-oncology has emerged to study the mechanism and prevention of cardiac dysfunction associated with cancer treatment. In this study, we investigated possible therapeutic effects of voluntary wheel running (VWR) on cardiac dysfunction observed in cancer-cachexia model mice established in our laboratory, since exercise therapy is known to be effective for patients with chronic heart failure.</p><p>【Methods】Mice were individually housed with free access to a wheel from 2 to 6 wks after implantation, to determine the effects of VWR on cancer cachexia-induced cardiac dysfunction.</p><p>【Results】VWR significantly suppressed the loss of heart and skeletal muscle weight as well as general symptoms of cachexia. Moreover, left ventricular ejection fraction significantly improved in cachexia group with VWR, compared to those without VWR. Microarray analysis revealed that the gene expression of “X”, which is an enzyme belonging to E3 ubiquitin ligase family but has not been reported to be related to heart failure, increased in the myocardium of cachexia mice, and that this increase was suppressed by VWR.</p><p>【Conclusions】These results suggest that the myocardial impairment associated with cancer cachexia may be caused by a different mechanism than that caused by heart failure, and that VWR may improve not only cachexia symptoms but also cachexia-induced cardiac dysfunction. In addition, the enzyme “X” may be one of key factors which are associated with myocardial atrophy and cardiac dysfunction on cancer cachexia. The pathway mediated by the enzyme “X” is currently being further analyzed.</p>