by Researchers at the University of Virginia School of Medicine have created an “atherosclerosis atlas” that provides a detailed understanding of the processes involved in the formation of plaque buildup, which can lead to heart attacks, strokes, and coronary artery disease (CAD). Atherosclerosis, also known as hardening of the arteries, affects around 50% of Americans aged 45 to 84, with many being unaware of their condition until a major cardiovascular event occurs.
The development of fatty plaques inside the arteries can impede blood flow and, when the plaques rupture, they can trigger life-threatening events such as heart attacks and strokes. To better understand the factors influencing plaque formation and stability, researchers have been keen to gain insights at the cellular level. This new study from the University of Virginia School of Medicine offers unprecedented insights that may pave the way for new treatments for atherosclerosis, CAD, and plaque prevention.
Lead researcher, Clint L. Miller, Ph.D., explained that to develop targeted treatments for specific disease processes, it is necessary to characterize gene expression patterns at the individual cell level. By mapping out these patterns, the researchers hope to develop strategies to prevent or reverse the disease and identify biomarkers that can assess a patient’s risk of developing clinical events.
The formation of atherosclerotic plaques involves various types of cells, including immune cells, smooth muscle cells, and endothelial cells. Tracking the composition and origin of these plaque-forming cells is challenging due to their transition into other cell types during plaque formation. To overcome this, Miller and his team, led by graduate student Jose Verdezoto Mosquera, created a comprehensive single-cell map of human atherosclerosis using nearly 120,000 cells from atherosclerotic coronary and carotid arteries. This map allowed the researchers to study the various cell subtypes within the plaques in detail.
The study also shed light on the changes that occur in smooth muscle cells during disease progression, including calcification (hardening) of the coronary arteries. The researchers identified two genes, LTBP1 and CRTAC1, that can serve as markers for the progression of atherosclerosis.
In addition to characterizing cell diversity, the researchers integrated their newly developed atherosclerosis single-cell reference with large-scale human genetic data. This integration allowed them to identify disease-causing cell types and subtypes, including fibroblast-like and lipid-rich smooth muscle cells.
The researchers believe that their atherosclerosis atlas is a crucial step towards developing targeted interventions for atherosclerosis and CAD. They also hope to identify biomarkers that can help prevent heart attacks and strokes, ultimately improving patient outcomes. Future iterations of the atlas will incorporate additional datasets from diverse patient populations and disease stages, enabling a more comprehensive understanding of the disease mechanisms and potential interventions.
By integrating data from the wider scientific community, the researchers aim to overcome biases in sampling and establish more robust disease mechanisms and interventions. This collaborative effort may lead to new strategies for treating atherosclerosis and reducing the risk of cardiovascular events.
