The Bidirectional Relationship between Cholesterol and Macrophage Polarization

Whether an atherosclerotic plaque progresses and eventually ruptures is heavily influenced by the function of macrophages. However, it is clear that a spectrum of macrophage phenotypes is present in the plaque, with some exhibiting stabilizing functions. While macrophages expressing characteristic M1 and M2 markers are evident, the disparate microenvironments of the plaque, such as regions of hemorrhage, promote other distinct macrophage phenotypes. Crucial to plaque development and progression is macrophage exposure to accumulated modified low density lipoproteins that leads to foam cell formation and development of the necrotic core. There are a range of biologically active compounds in low density lipoprotein (LDL) each having some bearing on which macrophage surface receptors are engaged and what cellular response ensues. Understanding the bidirectional interplay between ‘cholesterol’ and macrophage phenotype will provide valuable insight into key pathways to target which may possibly promote plaque stability by modulating macrophage function.