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The participation of circular RNA in cardiac remodeling induced by arterial hypertension: role of physical training in cardioprotection

Grant number: 23/16274-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2024
Effective date (End): January 31, 2027
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Edilamar Menezes de Oliveira
Grantee:Victor Hugo Antonio Joaquim
Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiovascular diseases continue to lead the global mortality ranking. Arterial hypertension is one of the main risk factors for the development of several conditions, including heart failure induced by cardiac remodeling. Associated with other mechanisms, the participation of non-coding RNA molecules (ncRNAs) act in the co- and post-transcriptional regulation of important cellular processes. In the family of ncRNAs, circular RNAs (circRNAs) are the most recently studied, with still little literature, however, with a promising ability to revolutionize the way diseases are identified and treated. CirRNAs mainly act by sequestering and degrading (sponging) microRNAs (miRNAs), modulating gene and, consequently, protein expression. Present in all the main guidelines related to cardiovascular health, physical exercise is considered one of the main non-drug therapies, with consolidated effectiveness in the literature. Despite the already known therapeutic potential, the study of its molecular mechanisms is recent, with a vast area of knowledge yet to be studied. Although the literature already demonstrates the involvement of circRNAs in arterial hypertension, their role in cardiac remodeling induced by hypertension lacks in-depth understanding, and the role of physical exercise in this context has not yet been described. The present research aims to explore this issue, investigating the expression and mechanisms of action of circRNAs found in sedentary and trained hypertensive hearts. For this, Spontaneously Hypertensive Rats (SHR) and their normotensive controls (Wistar-Kyoto rats) will be divided into sedentary SHR (SHR-S) and trained (SHR-T) and sedentary Wistar-Kyoto (WKY-S) and trained (WKY-T). The trained group will undergo an eight-week intervention of aerobic physical swimming training. In addition to functional and morphological tests, prior and subsequent, which prove the impact of the disease and the effectiveness of the intervention, the animals' hearts will be used to, through RNA sequencing analyses, identify and validate differentially expressed circRNAs, enabling the construction of a regulatory network (circRNA-miRNA-mRNA) for later verification in gain and loss of function studies, enabling the identification of signaling pathways that can explain the changes caused by hypertension and how physical exercise acted in this context. Finally, the knowledge generated from this effort increases the understanding of cellular processes that can contribute to the development of new therapeutic strategies for the control and treatment of hypertension and related complications.

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