The role of arterial smooth muscle cells in foam cell formation in atherosclerosis

Atherosclerosis, caused by cholesterol buildup and inflammation in arterial blockages (plaques), is the leading cause of death in Canadians. Cholesterol-loaded cells (foam cells) that collect in plaques make it unstable, leading to heart attacks and strokes. White blood cells called macrophages have previously been thought to be the main cell type accumulating cholesterol in plaques. However, our studies found that at least half of foam cells in human plaques come from artery smooth muscle cells.

Mouse models are routinely used to study and test new therapies for atherosclerosis, but little is known about the contribution of smooth muscle cells to foam cell formation in mouse plaques. Our finding calls into question whether these models are truly applicable to understand the human disease.

We will compare the contribution of smooth muscle cells to foam cell formation in two commonly used mouse models of atherosclerosis to that in human plaque. This will provide valuable information about the utility of those models for understanding atherosclerosis in humans.

Furthermore, we will examine the differences between macrophage-derived and smooth muscle cell-derived foam cells that are related to disease progression, regression, and treatment efficiency.

This research may change how we understand, prevent, and treat atherosclerosis.