Use of a new biosensor (PxIII-roGFP2) to study the redox signaling in mammalian cells in an atherosclerosis cenarium.

• Grant number: 23/14552-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 20, 2024
• End date: May 19, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Flavia Carla Meotti
• Grantee: Mikaela Peglow Pinz
• Supervisor: Paul Kenneth Witting
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Sydney, Australia
• Associated to the scholarship: 21/00349-0 - The genetically encoded biosensor (PxIII-roGFP) as a tool to monitor the production and role of organic peroxides in redox signaling in mammalian inflammatory cells, BP.PD

Abstract

The increased mortality rate linked to the pathogenesis of cardiovascular diseases (CVD) underscores the necessity to elucidate the precise molecular mechanisms that initiate conditions like atherosclerosis. Endothelial cells (ECs) play crucial roles in physiology and pathology, these cells are involved in maintaining vascular tone and can elicit increased inflammation and promote early stages of disease progression. This latter process leads to the production of reactive oxygen species (ROS) that oxidize LDL particles present into the sub endothelial space. Vascular smooth muscle cells (VSMCs) reside in the arterial medial layer and can engulf oxidized LDL, becoming foam cells. This may result in relocation of VSMCs to facilitate the uptake of oxidized LDL via LDL receptor and efflux back to circulation via ABCG1 transporter. This process is likely to induce a specific modification in EC signaling in a feed-back loop that defines an EC-VSMC axis in arterial vessels. Lipid peroxides, are important mediators of the inflammatory response and can act as cytotoxic mediators and/or signaling molecules. However, assessing the real-time cellular redox status remains highly challenging. Based on this, we are focusing research to characterize a novel biosensor to monitor the production and pathophysiological role of organic peroxides in mammalian vascular cells. The goal of the project is to utilize this innovative probe to improve our understanding of potential redox signaling mechanisms involved in the pathways governing EC-VSMCs interaction in a cellular co-culture system.