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Physical training-regulated microRNAs as potential biomarkers and therapeutics of doxorubicin-induced cardiotoxicity in Breast Cancer: in vivo study, in vitro in iPS-derived cardiomyocytes and clinical with patient analysis

Grant number: 22/02339-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2022
Effective date (End): August 31, 2024
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Edilamar Menezes de Oliveira
Grantee:Alex Cleber Improta Caria
Home Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiotoxicity promotes an increase in reactive oxygen species, inflammation, apoptosis, cardiac fibrosis, and these remain the main problems in the treatment of Cancer patients using doxorubicin. These associated processes induce myocardial dysfunction, decreasing the left ventricular ejection fraction, generating long-term heart failure. Some treatments have been described as attenuating these processes, including physical training. Evidence indicates that physical training can inhibit doxorubicin-induced cardiotoxicity, reducing the production of reactive oxygen species, minimizing the expression of pro-apoptotic and pro-inflammatory markers, reducing cardiac fibrosis, as well as preventing cardiopulmonary atrophy, increasing aerobic capacity and physical exertion, in addition to attenuating tumor growth. However, the molecular mechanisms that govern these benefits induced by physical training in this context remain largely unknown, mainly mechanisms associated with microRNAs, their target genes and signaling pathways. Thus, we propose to investigate the effects of aerobic physical training on the modulation of microRNAs in an animal model Of Breast Cancer treated with doxorubicin, for the identification of microRNAs as biomarkers and validation of a signaling pathway associated with cardiotoxicity, inflammation and apoptosis, which can be beneficially altered by physical training. Subsequently, the microRNA that was beneficially altered by physical training will be modulated in vitro in cardiomyocytes derived from human induced pluripotent stem cells and also analyzed in the peripheral blood of breast Cancer patients treated with doxorubicin. (AU)

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