Monocyte and macrophage foam cells in diabetes-accelerated atherosclerosis

Abstract

Diabetes results in an increased risk of atherosclerotic cardiovascular disease. This minireview will discuss whether monocyte and macrophage lipid loading contribute to this increased risk, as monocytes and macrophages are critically involved in the progression of atherosclerosis. Both uptake and efflux pathways have been described as being altered by diabetes or conditions associated with diabetes, which may contribute to the increased accumulation of lipids seen in macrophages in diabetes. More recently, monocytes have also been described as lipid-laden in response to elevated lipids, including triglyceride-rich lipoproteins, the class of lipids often elevated in the setting of diabetes.

Keywords: diabetes; foam cell; macropahge; monocytes; triglyceride-rich lipoprateins.

Figure 1

Monocyte and macrophage foam cells in diabetes. Foam cells may partly contribute to diabetes-accelerated atherosclerosis through changes in the myeloid cell compartment. In the setting of diabetes, both hyperglycemia and insulin insufficiency has been linked with increased monocyte lipid loading, macrophage lipid uptake, and cholesterol efflux. The effects of diabetes may, in part, be driven by increases in the expression of receptors that mediate lipid uptake, such as CD36, SR-A, LOX-1, and LPL (lipoprotein lipase), and or reductions in cholesterol efflux transporter (ABCA1, ABCG1). TLR4 can mediate the uptake of aggregated LDL. In addition, diabetes increases circulating and artery wall levels of triglyceride-rich lipoproteins (TRL) and their remnants, which are highly atherogenic. Figure created in part using BioRender.