Impact of the macrophages on the crosstalk with VSMCs in maintaining vascular calcification microenvironment: understanding the role of SIRT & cytokines

• Grant number: 22/06879-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date until: October 02, 2022
• End date until: September 30, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Willian Fernando Zambuzzi
• Grantee: Geórgia da Silva Feltran
• Supervisor: Maikel P. Peppelenbosch
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Erasmus University Rotterdam (EUR), Netherlands
• Associated to the scholarship: 19/22255-7 - Osteogenic markers and epigenetic reprogramming during the phenotypic transition of the vascular smooth muscle: from contraction to calcification, BP.DR

Abstract

It is timely to consider that cardiovascular diseases make up one of the major causes of death worldwide. The central role of vascular tissue has gained attention in recent years, mainly associated with increasing of aging. Vascular calcification, previously considered a passive degenerative condition of aging, is characterized by an ectopic deposition of inorganic calcium phosphate crystals in arterial tissue directly affecting the availability of nutrients. It is a pathology from a multifactorial etiology, where the causes are associated with physiological and environmental factors. Mesenteric ischemia is the interruption of secondary intestinal blood flow, which can cause disruption of the mucosal barrier, allowing the release of bacteria, toxins and vasoactive mediators, which in turn cause myocardial depression, a syndromic systemic inflammatory response (sepsis or septic shock), of multiple organs and death. We have investigated the molecular mechanism related in vascular smooth muscle cells calcification in vitro, and this is timely necessary to better understand the causes of it by investigating the molecular mechanisms driving the vascular mineralization once it may work as a biomolecular platform of markers able to conduct the eligible molecules to treat it, mainly considering the damage lead by the poor offer of oxygen. This project is therefore planned as an interdisciplinary network that will place the mesenteric ischemia at the center of the issue to be understood, considering performing of a set of technical skills able to be grouped into 2 research work packages (WP) that will investigate the multiple interactions between macrophages and vascular smooth muscle cells (VSMCs). (AU)