Understanding the role of alternative macrophage phenotypes in human atherosclerosis.

Atherosclerosis-based ischemic heart disease is still the primary cause of death throughout the world. Over the past decades there has been no significant changes in the therapeutic approaches to atherosclerosis, which are mainly based on lipid lowering therapies and management of comorbid conditions such as diabetes and hypertension. The involvement of macrophages in atherosclerosis has been recognized for decades. More recently, a more detailed and sophisticated understanding of their various phenotypes and roles in the atherosclerotic process has been recognized. This new data is revealing how specific subtypes of macrophage-induced inflammation may have distinct effects on atherosclerosis progression and may provide new approaches for treatment, based upon targeting of specific macrophage subtypes. We will comprehensively review the spectrum of macrophage phenotypes and how they contribute to atherosclerotic plaque development and progression. Various signals derived from atherosclerotic lesions drive macrophages into complex subsets with different gene expression profiles, phenotypes, and functions, not all of which are understood. Macrophage phenotypes include those that enhance, heal, and regress the atherosclerotic lesions though various mechanisms. Targeting of specific macrophage phenotypes may provide a promising and novel approach to prevent atherosclerosis progression.