Effects of aerobic exercise training on cardiac muscle in cancer-induced cachexia

Author(s)

Larissa Gonçalves Fernandes

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2020-05-19

Examining board members

Patricia Chakur Brum

• Advisor: Patricia Chakur Brum

Abstract

Cancer cachexia-induced cardiac damage has become an important issue to survival management and quality of life in cancer patients. Since aerobic exercise training (AET) has been shown to reduce the negative effects of heart failure and other comorbidities, its use as preventive or therapeutic tool has considered a reasonable intervention for cancer-induced cardiac dysfunction. In this master dissertation, we aimed to investigate the impact of cancer cachexia and previous AET on cardiac function and structure using a colon adenocarcinoma cells 26 (CT26). AET consisted of 45 days, 60 minutes/session at 60% of maximal speed, and 5 days per week. Cardiac function was assessed by two-dimensional guided M-Mode echocardiography and cardiac structure was evaluated by light microscopy. The protein expression levels of mitochondrial complex (I, II, IV and V) were analyzed by western blotting. The mRNA levels of TGF-beta1 and Smad-2/3 were analyzed by quantitative Real-Time PCR. Our data confirm CT26 tumor-bearing mice as a well-characterized model of cancer cachexia with body-weight loss, skeletal muscle atrophy, splenomegaly and pulmonary edema. CT26 bearing mice exhibited cardiac atrophy, cardiac dysfunction and remodeling characterized by impaired left ventricle ejection fraction associated with increased cardiac collagen deposition and reduced cardiac myocyte´s diameter. Indeed, CT26 tumor-bearing mice showed reduced complex IV mitochondrial proteins levels, increased TGF-beta1, SDHA and reduced Smad2 mRNA levels. AET was efficient in attenuating the reduced complex IV and re-establishes complex II toward control levels with no impact on left ventricle ejection fraction and cardiac atrophy. Interestingly, AET led to significant anti-cardiac remodeling effect by reducing cardiac collagen deposition and inflammation associated to reduced levels of TGF-beta1 and oxidative metabolism improvement. Taken together, our study provides evidence for cardiac dysfunction and remodeling in CT26 model. The effects of AET in attenuating cardiac fibrosis and inflammation provide mechanistic insights by which AET can help counteracting cachectic conditions that severely affects cardiac muscle (AU)

• FAPESP's process: 16/22835-5 - Effects of voluntary physical activity on cardiac function and structure in animal models of cancer cachexia
• Grantee: Larissa Gonçalves Fernandes
• Support Opportunities: Scholarships in Brazil - Master