ReviewMonocyte recruitment and foam cell formation in atherosclerosis
Introduction
It has been recently appreciated that atherosclerosis is a chronic immune-inflammatory disease in which the interaction of monocytes with activated luminal endothelium is a crucial event leading to atherosclerotic alteration of the arterial intima (Hansson, 2001, Hansson, 2005, Hansson et al., 2002, Libby, 2002, Wick et al., 2004). Monocytes migrate into the subendothelial layer of the intima where they differentiate into macrophages or dendritic cells (Gerrity, 1981a, Ross, 1993, Bobryshev, 2005a). In the subendothelial space enriched with atherogenic lipoproteins (Skalen et al., 2002, Williams and Tabas, 2005), most macrophages transform into foam cells (Gerrity, 1981a, Ross, 1993). Foam cells aggregate to form the atheromatous core and as this process progresses, the atheromatous centres of plaques become necrotic, consisting of lipids, cholesterol crystals and cell debris (Ross, 1993, Stary et al., 1994, Stary et al., 1995, Takahashi et al., 2002). This review highlights some structural aspects of monocyte recruitment and foam cell formation in atherosclerosis.
Section snippets
Adhesion and migration of monocytes through the arterial luminal endothelium
In the pre-atherosclerotic stage, a large number of blood cells, predominantly monocytes and T-cells, become attached to the luminal endothelium in atherosclerosis-predisposed areas of the arteries (Fig. 1A–C) (Babaev et al., 1993, Bobryshev and Lord, 1995). The continuously increasing adhesion of monocytes and T-cells to the luminal endothelium is a hallmark of the early stages of the development of atherosclerotic lesions (Ross, 1993, Hansson, 2001, Hansson, 2005, Hansson et al., 2002, Libby,
Recruitment of monocytes and dendritic cells in advanced atherosclerosis
In developed atherosclerotic plaques, fibrous caps form to separate the necrotic cores. Morphological studies have revealed that the fibrous caps contain only a few macrophages, dendritic cells and T-cells, suggesting that the invasion of monocytes/macrophages, dendritic cells and T-cells from the arterial lumen into plaques is dramatically reduced (Bobryshev and Lord, 1998, Bobryshev et al., 1999). It has been shown that both dendritic cells and T-cells in developed plaques are present mostly
Mechanisms of foam cell formation
In the arterial wall, macrophages react to the plaque microenvironment by internalising and metabolising a variety of subendothelial components (Williams and Tabas, 2005, Skalen et al., 2002, Itabe, 2003). Some lipoproteins infiltrating the arterial wall become trapped in the intima by matrix components and become modified (Hevonoja et al., 2000, Oorni et al., 2000, Williams and Tabas, 2005, Skalen et al., 2002, Itabe, 2003). ox-LDL are formed through enzymatic and non-enzymatic oxidation (
Concluding remarks
The importance of monocytes in atherosclerosis is well recognised. In the early stages of the development of atherosclerotic plaque, monocytes enter the arterial intima through the luminal endothelial monolayer but when the plaque matures, monocyte may enter the plaque through neovascularisation. Much knowledge has been gained about the molecular mechanisms of monocyte recruitment into the intima from the bloodstream but the fate of monocytes after they enter the arterial wall is not yet well
Acknowledgements
I wish to thank the St Vincent's Clinic Foundation, Sydney, for continued support.
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