The Effect Of Voluntary Exercise On Cardiac Remodeling In Apc Min/+ Mice

Abstract

ApcMin/+ mice experience intestinal adenomas and chronic inflammation that lead to cachexia and cardiac enlargement. Physical activity can maintain overall physical function, lower chronic inflammation and attenuate cardiac enlargement. PURPOSE: To determine whether lifetime voluntary exercise attenuates cardiac enlargement and related changes in gene expression in ApcMin/+ mice. METHODS: C57BL/6 (wt) and ApcMin/+ mice given access to running wheels or served as cage controls beginning at 4 wks of age and mice were sacrificed at 26 wks of age. Body weights, heart, gastrocnemius, mammary fat pads, and spleens wts were determined and hearts were frozen. Collagen 1a, TGFb, myosin heavy chain (MHC)a, and MHCb were determined by RT-PCR. STAT3 activation was determined by western blot analysis. RESULTS: Body wts were 10% lower in ApcMin/+ than wt mice (21.5±.5 vs 24.2±.7 g) (P≤0.05) and were not altered by exercise. Gastrocnemius muscle wts were 37% lower in ApcMin/+ than wt mice (68±5 vs 108±4 mg) (P≤0.05) but were not altered by exercise. Mammary fat pad wts were lower in ApcMin/+ than wt mice (28±11 vs 262±49 mg) (P≤0.05), and were not altered by exercise. Heart wts were 25% heavier in ApcMin/+ than wt mice (9.0±.3 vs 7.6±.3 mg/mm) (P≤0.05) but were not altered by exercise. Procollagen 1a gene expression was 300% greater in ApcMin/+ than wt mice (3.6±.9 vs 1±.1) (P≤0.05), but exercise attenuated this expression by 48% in ApcMin/+ mice (1.9±.2) (P≤0.05). MHCa gene expression was not different between ApcMin/+ and wt mice, nor was it altered by exercise. However, MHCb gene expression was attenuated by exercise in both ApcMin/+ and wt mice (0.5±.1 vs 1±.1) (P≤0.05) but was not different between ApcMin/+ and wt mice. CONCLUSIONS: These results demonstrate that increased exercise altered cardiac extracellular matrix and myocyte gene expression. The exercise-induced changes altered the physiological function of the heart during cancer-cachexia that were independent of heart and body weight in ApcMin/+ mice.