Characterization of platelet adhesion markers and ZFP36 expression in endothelial cell cultured in low and high Zn2+ media

• Grant number: 24/22073-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Stephen Fernandes de Paula Rodrigues
• Grantee: João Victor Santos Pinheiro
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Stroke and other diseases in which thrombus formation play an important role are the leading cause of morbidity and mortality from cardiovascular diseases. These conditions share a common feature, dysregulation of the blood coagulation process. Several studies report the involvement of divalent metal ions, such as zinc ion (Zn²¿), in modulating these pathways. Zn²¿ is secreted by active platelets and is predominantly found within the cell nucleus. The presence of Zn²¿ in the nuclear region indicates its participation in fundamental cellular processes, such as proliferation, signal transduction, and transcription. An important protein that has zinc finger domains necessary for stabilizing its structure and regulating its function are the Zinc-Finger Proteins (ZFPs). The ZFP 36 can regulate the expression of genes important for the anti-inflammatory pathway and endothelial cell growth. Considering that changes in extracellular Zn²¿ concentrations can interfere in blood coagulation and platelet activation, we hypothesize that high extracellular concentrations of Zn²¿ increase the expression of adhesion molecules in endothelial cells (ECs), favoring thrombus formation and stabilization by negatively regulating the expression of ZFP36. To validate our hypothesis, we will evaluate whether high concentrations of extracellular Zn²¿ and those derived from activated platelets can modulate platelet aggregation and the expression of adhesion molecules, with a consequent reduction in the expression of ZFP36 in human umbilical vein endothelial cells (HUVECs), measured by flow cytometry and Western blot techniques.