Figure 1

The initiation of an atherosclerotic lesion is characterized by retention of LDL and subsequent oxidative modification (oxLDL) within the matrix of the vascular intima. Stimulation of the overlying endothelial cells by oxLDL recruits monocytes from the circulation to the vessel wall. Differentiation of monocytes into macrophages and scavenger receptor mediated uptake of oxLDL aggregates results in the formation of foam-cells. Upon stimulation vascular smooth muscle cells (VSMC) migrate and proliferate. Tissue factor is expressed on macrophages and VSMCs within the advanced lesion and is likely to be involved in the conversion of accumulated fibrinogen into fibrin, although fibrin polymerization can be facilitated by other enzymes than thrombin. Furthermore, VSMCs and macrophage derived apoptotic bodies exposing TF probably contribute in thrombin formation. Considering atherosclerosis as a chronic inflammation, the inflammatory drive leads to IL-6 induced TF expression of circulating monocytes and the formation of microparticle exposing TF in the circulation, maintaining a certain level of thrombin production and fibrin formation. Increased circulating D-dimer levels are thus the result of fibrin proteolysis in both circulation and the advanced atherosclerotic lesion.