Antibodies targeting angiotensin 2 Type 1 receptor as a putative mediator of driving endothelial dysfunction

This research project focuses on the kinase activity profiling of autoantibody-mediated signaling involving the angiotensin II type 1 receptor (AT1R) in endothelial and immune cells. AT1R, a member of the G protein-coupled receptor (GPCR) family, plays a central role in regulating vascular tone, extracellular matrix generation, fibrosis, and inflammation. This receptor is expressed on the surface of various immune cells such as endothelial cells and monocytes. The binding of these autoantibodies to AT1R on cells engages kinase activity, leading to inflammatory responses and increased expression of adhesion molecules and cytokines. This project aims to 1) Validate Pamgene data for high-throughput analysis of kinase activities in endothelial and monocytes stimulated with AT1R antibodies; 2) Assess changes in the expression of adhesion molecules and reactive oxygen species (ROS) production; and 3) Evaluate the effect of AT1R antibodies on neutrophil and monocyte adhesion to endothelial cells. These findings will advance the understanding of how AT1R antibodies contribute to SSc pathogenesis and could inform new therapeutic approaches targeting these pathways.