By inventing and deploying a novel single-cell sequencing technique that potentially improves upon those already in use, researchers at the University of Chicago Medicine have discovered new potential therapeutic targets to treat atherosclerosis and coronary artery disease. The research will assist other scientists in evaluating single-cell genetic data more efficiently as a result of this technique, which will help them better understand coronary artery disease and other disease states and biological systems.
The researchers utilized their cardioinformatics pipeline to discover novel types of vascular cells produced from smooth muscle cells located in the walls of arteries and information on how those cells communicate. Traditional risk factors for heart disease, such as excessive cholesterol or blood pressure, are targeted by most presently authorized medications for heart disease.
Atherosclerosis is the buildup of plaque inside or along the walls of arteries, and it is a process that worsens with age. Blood flow can be restricted or obstructed when plaque, made up of fatty components like cholesterol, inflames and hardens the vessel walls. Atherosclerosis is the main reason of heart attacks and strokes, both of which can be fatal.
The team used a modeling technique called RNA-trajectories and discovered that Other types of cells are produced by vascular smooth muscle cells, including cells that look like fibroblasts and chondrocytes. It can express signs of inflammation and extracellular matrix degradation, which are warning signs of atherosclerosis.
Several already-approved medications were shown to be capable of inhibiting communication between smooth muscle cells and fibroblast cells, according to the researchers. They discovered numerous chemotherapies that target the epidermal growth factor receptor (EGFR) signaling cascade and have the potential to be repurposed to inhibit erroneous signaling and inflammation in a variety of cell types.
Discovering how cells communicate with one another should help scientists better grasp the complexity of atherosclerosis and how plaque forms; the next step would be to test the medications’ efficacy in preclinical and clinical studies.
While the research is the first step in developing a novel treatment, these types of computer-assisted in silico tests can provide light on potential combination therapies or reduce possible side effects by focusing on cell-type-specific activities in the heart and vasculature.
Apart from atherosclerosis and coronary artery disease, the workflow can be applied to research on other conditions. It is anticipated that scientists working in disciplines like cancer and neurological illnesses would use the method to create testable biological hypotheses using their information.
The team also created PlaqView, an open-source, interactive online application that allows users with no prior coding experience to view datasets and compare single-cell RNA sequencing methods.
Story Source: Ma, W. F., Hodonsky, C. J., Turner, A. W., Wong, D., Song, Y., Mosquera, J. V., … & Miller, C. L. (2022). Enhanced single-cell RNA-seq workflow reveals coronary artery disease cellular cross-talk and candidate drug targets. Atherosclerosis, 340, 12-22. DOI: https://doi.org/10.1016/j.atherosclerosis.2021.11.025