Ethanol effects on cardiovascular system: the role of gut microbiota and fMLP/FPR-1

• Grant number: 22/12426-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: March 31, 2023
• End date: March 30, 2024
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Carla Brigagão Pacheco da Silva
• Supervisor: Camilla Ferreira Wenceslau
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of South Carolina, United States
• Associated to the scholarship: 20/11339-2 - Trimethylamine N-oxide (TMAO) as a link among gut dysbiosis, immune system activation and vascular dysfunction induced by ethanol consumption, BP.PD

Abstract

Cardiovascular diseases (CVDs), a group of disorders that affect the heart and blood vessels, represent the leading cause of mortality and disability worldwide. Excessive ethanol consumption is an important public health concern, and it is a risk factor for CVDs. Despite extensive investigation, mechanisms underlying cardiovascular dysfunction induced by ethanol are not fully known. Eubiosis and dysbiosis are related to healthy and disease status of the gut microbiota, respectively. The strong association between the gut microbiota and the immune system suggests a potential role for the gut microbiota in CVDs- and ethanol-induced injuries. In this context, the activation of the immune system contributes to the development and progression of CVDs, and most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle induce gut dysbiosis. N-formyl peptides (NFPs), such as N-formyl-methionyl-leucyl-phenylalanine (fMLP), are released by tissue bacteria, and attract and activate circulating blood leukocytes by binding to specific G-protein coupled receptors (GPCR) on these cells, directing the inflammatory response to sites of infection/inflammation. fMLP also modulates vascular tone, and formyl peptide receptors (FPRs), such as FPR-1, activates immune responses, indicating that fMLP/FPRs may be important in CVDs. This study will investigate whether gut dysbiosis and fMLP/FPR-1 activation contribute to ethanol-induced vascular dysfunction. (AU)