Macrophage complexity in human atherosclerosis: opportunities for treatment?

The pivotal role of macrophages in experimental atherosclerosis is firmly established, but their contribution to human disease is less well defined. In this review we have outlined the current insights on macrophage phenotypes and their presumed precursors, monocytes, in clinical atherosclerosis, and their association with disease progression. Moreover, we will assess major clinical modifiers of macrophage-mediated plaque inflammation and define the outstanding questions for further study.

Our survey indicates that macrophage accumulation and status in human plaques are linked with lesion progression and destabilization as well as with symptomatic coronary artery disease. Likewise, levels of their precursors, circulating monocytes were repeatedly seen to associate with atherosclerosis and to predict clinical outcome. Furthermore, the presence and phenotype of both macrophages and monocytes appears to be responsive to the traditional risk factors of atherosclerosis, including hypercholesterolemia, hypertension, and type 2 diabetes, and to treatment thereof, with clear repercussions on disease development.

Although plaque macrophages and their precursor cells do represent attractive targets for treating cardiovascular diseases, this therapeutic avenue requires much deeper understanding of the complexity of macrophage biology in human atherosclerosis than available at present.