Role of Long Non-Coding RNAs (lncRNAs) in Cell-Cell Communication and Extracellular Matrix in Post-Myocardial Infarction

• Grant number: 24/04572-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 30, 2024
• End date: May 29, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Eduardo Krieger
• Grantee: Caio Mateus da Silva
• Supervisor: Evangelia Petsalaki
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: European Bioinformatics Institute, England
• Associated to the scholarship: 21/08797-1 - Identification and characterization of long non-coding RNAs (lncRNAs) that modulate cardiac extracellular matrix, BP.DR

Abstract

Introduction: Myocardial infarction (MI), a leading cause of mortality globally, initiates cardiac repair mechanisms leading to extracellular matrix (ECM) deposition and subsequent cardiac fibrosis. Post-MI, the heart undergoes significant cellular and molecular alterations, impacting cellular interactions. Within the methods of advanced therapeutic strategies, long non-coding RNAs (lncRNAs) emerge as critical regulators of gene expression, showing promise in MI treatment due to their influence on cellular communication and ECM modulation. Objective: This study aims to elucidate the role of lncRNAs in modulating cell-to-cell communication and their subsequent impact on the ECM post-infarction. Methods: Our approach involves a reanalysis of single-cell RNA sequencing (scRNA-seq) data from Kuppe et al., 2022, (31 samples collected from various cardiac regions of 23 patients, ranging from 3 to 150 days post-infarction) focusing on extracting cell-type-specific signaling networks. We will employ network propagation methods and analyze cell-cell communication through ligand-receptor interactions to identify co-regulated lncRNA-RNA pairs post-MI. Additionally, we will apply inference methods to deduce the regulatory functions of lncRNAs within these networks. The ultimate goal is to uncover alterations in cell-cell interaction networks, particularly in fibroblasts, and identify lncRNAs associated with ECM remodeling processes post-MI.