Deciphering the Crosstalk within Human Coranary Atherosclerosic Plaques

We are investigating the cross-talk between T cells and the coronary atherosclerotic plaque microenvironment using single-cell technologies. Coronary disease is a chronic inflammatory disorder characterized by plaque build-up in arteries. Understanding the signaling pathways between T cells and other nonimmune cells within the atherosclerotic plaque could lead to the development of novel therapies to prevent atherosclerotic progression and its potentially deadly complications, (i.e., heart attacks and strokes). After dissecting human coronaries from donor hearts, we digested the coronary arteries into single cell suspension, sorted cells using FACS (fluorescence-activated cell sorting), and used 10X genomics to analyze their single-cell gene expression. Our preliminary analysis of the ligand-receptor interactions suggests that T cells communicate with myeloid and smooth muscle cells within the plaque. Analysis by immunohistochemistry reveals that memory T cells predominate in theplaque, suggesting T cells may have been recruited by interaction with myeloid that display cognate peptide epitopes that transform naive T cells into memory T cells. In vitro analysis of the interaction of T cell cytokines with smooth muscle cells shows upregulation of proinflammatory and profibrotic pathways. In conclusion, we find that T cells appear to communicate with myeloid and smooth muscle cells within coronary atherosclerotic plaques.In the future, we plan to validate a model in-vitro that could lead to the discovery of therapeutic treatments for atherosclerosis.