Expression profile of lncRNAs in the search for a therapy for heart failure of ischemic etiology: role of aerobic exercise training

• Grant number: 22/15483-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Tiago Fernandes
• Grantee: Bruno Rocha de Avila Pelozin
• Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Aerobic exercise training (AET) is known for its ability to attenuate the deleterious effects of myocardial infarction (MI) and heart failure (HF) as well as to increase survival in patients with heart disease. However, there is still alarge gap in the literature on the therapeutic effects of AET and the participation of long non-coding RNAs (lncRNAs) in cardiovascular diseases (CVDs). lncRNAs have been shown to be an important regulator of thepathophysiological mechanisms of CVDs, including MI, particularly by transcriptional modulation of genes involved in fibrosis, angiogenesis, apoptosis, and cardiac hypertrophy, which are responsible for the progression to HF.These transcripts can promote or repress gene transcription, through signaling and interaction with RNA-binding proteins, acting directly or through chromatin remodeling complexes; modulating the dynamics and epigeneticcontrol of transcription of specific genes; and for the synthesis of micro peptides. Currently, due to their stability, they are considered important biomarkers in CVDs. However, few studies have investigated the effects of AET onthe modulation of lncRNAs in HF and its effects on cardiac morphology and function. Given the above, we will explore the role of AET in lncRNAs modulation in Wistar rats with ischemic HF. Firstly, the HF model will beestablished, followed by cardiac morphological, functional, and metabolic analyses. Subsequently, through large-scale analysis (RNA sequencing), the profile of the lncRNAs expressed in the remaining area of the left ventricularinfarction of sedentary sham (SS), trained (ST), sedentary infarcted (SI), and trained infarcted (TI). Those lncRNAs modulated in IM and altered by TFA will be identified, in particular looking for those normalized patternsof the SS or ST groups. Through bioinformatics analysis, the target microRNAs of the lncRNAs, regulated genes, and the signaling pathways involved will be identified. For an in vitro study, in cultured cardiomyocytes, a lncRNAmodulated by TFA will be selected to validate its beneficial effects against pathological stimulation with isoproterenol. With that, a better understanding of lncRNAs and their regulation of pathological processes in HF ofischemic etiology can promote the discovery of new targets and make room for new therapeutic strategies.