REVIEW

Monocytes in atherosclerosis: subsets and functions Kevin J. Woollard and Frederic Geissmann Center for Molecular and Cellular Biology of Inflammation (CMCBI), Division of Immunology, Infection and Inflammatory Diseases (DIIID), 1st Floor New Hunts House, Guys Campus, London SE1 1UL, UK Correspondence to: K. J. Woollard ; Email: kevin.woollard@kcl.ac.uk Abstract Chronic inflammation drives atherosclerosis, the leading cause of cardiovascular disease. Over the past two decades, data have emerged showing that immune cells are involved in the pathogenesis of atherosclerotic plaques. The accumulation and continued recruitment of leukocytes are associated with the development of ‘vulnerable’ plaques. These plaques are prone to rupture, leading to thrombosis, myocardial infarction or stroke, all of which are frequent causes of death. Plaque macrophages account for the majority of leukocytes in plaques, and are believed to differentiate from monocytes recruited from circulating blood. However, monocytes represent a heterogenous circulating population of cells. Experiments are needed to address whether monocyte recruitment to plaques and effector functions, such as the formation of foam cells, the production of nitric oxide and reactive oxygen species, and proteolysis are critical for the development and rupture of plaques, and thus for the pathophysiology of atherosclerosis, as well as elucidate the precise mechanisms involved. Introduction Atherosclerosis is a multifaceted, progressive, inflammatory disease that affects mainly large and mediumsized arteries. It is characterized by the formation and build-up of atherosclerotic plaques that consist of a well-defined structure of lipids, necrotic cores, calcified regions, inflamed smooth muscle cells, endothelial cells, immune cells and foam cells; consequently, atherosclerosis is associated with cardiovascular disease.1 In the 1970s, details of a comprehensive scheme of ‘response-to-injury’ began to emerge,1 in which endothelial activation is initiated by various triggers, such as altered blood rheology, modified LDL, increased homocysteine levels, and inflammation induced by bacterial antigens and membrane components. The presence of leukocytes within atherosclerotic arteries was characterized in the early 1980s.2 Initially, macrophages were reported as the predominant cell type present within atherosclerotic vessels, but T cells, B cells, neutrophils, mast cells, dendritic cells (DCs) and monocytes have all been observed in both mouse and human aortas.3-5 Transgenic mouse models have allowed researchers to directly investigate the molecular mechanisms that underlie the development of atherosclerosis.6 The roles of cell adhesion molecules, chemokines, cellular mediators and signaling molecules involved in lymphocyte and monocyte/macrophage activation, and the progression of atherosclerosis, have been described elsewhere.3-7 This Review focuses on monocyte biology in relation to atherosclerosis, and specifically discusses the recruitment of blood monocytes to plaques and their relationship with plaque macrophages. Whether and how distinct functional subsets of monocyte might have different roles in the pathogenesis of atherosclerosis is also discussed. SEE ARTICLE