MicroRNAs as potential targets for treatment of obesity-induced cardiac hypertrophy

• Grant number: 23/03444-9
• Support Opportunities: Scholarships abroad - Research
• Start date: July 15, 2023
• End date: July 14, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Gabriela Placoná Diniz
• Grantee: Gabriela Placoná Diniz
• Host Investigator: Dazhi Wang
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of South Florida (USF), United States

Abstract

Obesity is a chronic multisystem disease associated with increased morbidity and mortality. Obesity is capable of producing a variety of hemodynamic, neurohormonal, and metabolic alterations that may affect heart morphology and function, leading to cardiac hypertrophy and myocardial dysfunction. MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of specific target mRNAs by inhibiting mRNA translation or promoting mRNA decay. Several studies have demonstrated the role of individual miRNAs in the development and progression of cardiac diseases. We have previously shown that the miRNAs expression profile is changed in obesity-induced cardiac hypertrophy in male mice. In addition, we reported that obesity-associated myocardial hypertrophy in female mice is accompanied by alterations of some miRNAs. Although miRNAs play a key role in cardiac hypertrophy and myocardial dysfunction caused by diverse stimuli, the impact of miRNAs in obesity-induced myocardial hypertrophy remains largely unknown. In this study, we propose to identify miRNAs commonly dysregulated in obesity-induced cardiac hypertrophy in both sex with enrichment of pathways related to myocardial hypertrophy. Then, we propose to use adeno-associated virus (AAV) delivery system to mediate miRNA knockdown or overexpression into myocardial tissue in order to determine the impact of miRNAs in obesity-related cardiac hypertrophy. (AU)