Cardiac Enlargement in a Mouse Model of Intestinal Cancer

Abstract

1233 Cancer-induced cachexia is a life-threatening wasting syndrome characterized by reduced body mass and decreased antioxidant defense systems. This condition is often associated with the activation of the immune system and also heart failure. PURPOSE: To characterize cardiac muscle remodeling in a cachexic mouse model induced by intestinal tumors. The APC+/− mouse used in this study has a high incidence of intestinal tumor formation. We hypothesized that these cachexic mice would have altered heart remodeling. METHODS: Female C57BL6 (CON, n = 7) and APCmin+/− (MIN, n = 7) mice, 6–8 months of age, were monitored for daily food intake. Animals were sacrificed and liver, heart, and tibias were excised. Liver catalase (CAT) activity was measured spectrophotometrically. Cardiac α-myosin heavy chain and 18S mRNA abundance were analyzed by RT-PCR. RESULTS: CON and MIN ate similarly (p>0.05), but MIN BW was decreased by 20.5% (p<0.05). MIN CAT was decreased 54% compared to CON. The heart weight:tibia length ratio was significantly increased 27% in MIN compared to CON (p<0.05). Cardiac α-myosin heavy chain, corrected with 18S and normalized to CON was decreased 40% in MIN (p = 0.045). CONCLUSIONS: Cachexic female APCmin+/− mice, as described by decreased body weight with normal eating behavior as well as decreased catalase activity, suffer from cardiac hypertrophy with altered remodeling. While the stimulus of cardiac enlargement in this cachexic model is not certain, blood volume expansion and atrial natriuretic peptide signaling may be important mechanisms for the induction of this cardiac enlargement. This study was funded by the Colorectal Cancer COBRE program from the National Institute of Health/USC.