Effect of the association between arterial hypertension and Walker-256 cancer on cardiac phenotype and tumor progression: therapeutic potential of aerobic exercise.

Author(s)

Luis Felipe Rodrigues

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
• Defense date: 2024-04-05

Examining board members

Tiago Fernandes; Patricia Chakur Brum; Lígia de Moraes Antunes Corrêa; Luciana Venturini Rossoni

• Advisor: Tiago Fernandes

Abstract

Cardiovascular diseases (CVD) followed by cancers are the leading causes of death worldwide; recognized for being complex and multifactorial diseases that share common risk factors and interactions. In recent decades, cardio-oncology has focused on the prevention and treatment of CVD in cancer survivors, stemming from the cardiotoxicity of antineoplastic agents. On the other hand, there is a growing body of epidemiological evidence demonstrating that CVD acts as pro-oncogenic factors, as patients with CVD have a higher incidence of cancer compared to healthy populations. A significant association between arterial hypertension (AH) and cancer incidence/mortality in humans has been described. It is possible that the bidirectional relationship of these diseases may potentiate cardiac damage, yet little is known about their association and the mechanisms related to this phenomenon. Aerobic exercise (AE) has been used as an important non pharmacological therapy to alleviate symptoms, improve exercise tolerance, quality of life, and reduce hospitalization for patients with CVD and cancer. However, the effects of APT on cardiac repercussions in the association of CVD with cancer are unknown. Thus, the aim of this study was to investigate the association between AH and cancer in cardiac phenotypic alterations and tumor progression in rats and to verify the therapeutic role of AE on cardiomyopathy and functional impairment induced by the bidirectional relationship between the diseases. Both the AH model with spontaneously hypertensive rats (SHR) and the cancer model with Walker-256 tumor were selected due to the similarity of their pathophysiology in humans. 50 Wistar Kyoto rats and 50 SHR were used. Walker-256 carcinoma implantation was performed in the subcutaneous tissue of the right flank region. The animals were trained for 6 weeks, 60-minute sessions, once a day, 5 times a week, with a gradual increase in workload. The following were evaluated: blood pressure and resting heart rate, maximum physical exertion tolerance, ventricular function and structure, tumor growth, cardiac and skeletal muscle mass, percentage of cachexia, and citrate synthase enzyme activity. We also measured cardiomyocyte diameter, cardiac fibrosis, and capillary-to-fiber ratio by histological methods. Expression of genes for pathological cardiac hypertrophy and collagen content, miRNA-208 family, and protein expression analysis for survival pathways and cellular apoptosis. Statistical analyses were performed using GraphPad Software (California, USA) (AU)

• FAPESP's process: 21/06229-6 - Effect of the association between arterial hypertension and Walker-256 cancer on the cardiac phenotype and tumor progression: therapeutic potential of aerobic exercise training
• Grantee: Luis Felipe Rodrigues
• Support Opportunities: Scholarships in Brazil - Master