Rôle de l'interaction monocytes-cellules endothéliales dans la formation, le développement et les complications de la plaque d'athérome

Abstract

80% of all leukocytes found in atheroma plaque are monocytes, while 5 to 20% are lymphocytes. This key feature is, at least in part, linked to the specificity of the adhesion molecules expressed by the components of the plaque. Monocyte recruitment is mediated by their selective interaction with the damaged vascular endothelium. The underlying molecular mechanism is coordonated expression, by the two cell types, of adhesion molecules (selectins, integrins, and members of the immunoglobulin superfamily), in response to hemodynamic and biochemical factors responsible for endothelial damage. The monocyte-endothelial cell interaction can schematically be broken down into three steps: monocyte rolling along the vascular endothelium, followed by firm adhesion and transmigration towards the subendothelium. Monocytes become macrophages in the subendothelium, where they engulf oxidized LDL, thereby being transformed into foam cells; in conjunction with T lymphocytes they form fatty streaks, which are the first observable signs of atheroma formation. Monocyte adhesion to endothelial cells is also followed by selectin/integrin-mediated triggering of intracellular signals that modulate the functions of one or other cell type. NF-kB activation has been shown to trigger the expression of genes encoding chemokines, proinflammatory cytokines and tissue factor. Monocytes-macrophages are thus involved not only in the formation but also in the development and complications (rupture and thrombosis) of atheroma plaque. This suggests that therapeutic interventions targeting macrophage participation in atherogenesis might give interesting results.