lncRNA Modulation and Its Morphological, Functional, and Metabolic Effects in Cardiomyocytes

• Grant number: 25/20025-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 01, 2026
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Tiago Fernandes
• Grantee: Bruno Rocha de Avila Pelozin
• Supervisor: Dazhi Wang
• Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of South Florida (USF), United States
• Associated to the scholarship: 22/15483-6 - Expression profile of lncRNAs in the search for a therapy for heart failure of ischemic etiology: role of aerobic exercise training, BP.DR

Abstract

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Ischemic heart disease frequently progressing to heart failure (HF), is a syndrome characterized by adverse cardiac remodeling, metabolic dysfunction, and poor clinical outcomes. Aerobic exercise training (AET) is widely recognized as a non-pharmacological intervention approach that mitigates pathological remodeling and improves cardiac function in HF. However, the molecular mechanisms underlying these effects remain incompletely understood. Emerging evidence highlights long non-coding RNAs (lncRNAs) as key regulators of cardiac physiology and pathophysiology. Our preliminary findings identified differentially expressed lncRNAs in an experimental HF model, several of which were restored to control levels following AET.The present project aims to investigate the role of lncRNA NONRATT015204.2 modulation on morphological, functional, and metabolic adaptations in cardiac cells. To achieve this, neonatal rat ventricular cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) will be used as complementary models. Gain- and loss-of-function approaches will be employed through siRNA-mediated silencing and adenoviral/AAV9-based overexpression. Subsequent analyses will assess hypertrophy, cell viability, proliferation, apoptosis, and metabolic remodeling, alongside molecular profiling of pathways regulated by lncRNA NONRATT015204.2 . The cardioprotective potential of lncRNA NONRATT015204.2 modulation will also be evaluated under pathological stress induced by phenylephrine. This study will provide novel insights into the regulatory role of lncRNAs in exercise-mediated cardioprotection, and the results are expected to contribute to the identification of innovative therapeutic targets for HF.