1. Lipid core constitution Activated macrophages accumulate lipids
Figure 22 Excessive atherogenic lipoproteins penetrate the intima from the bloodstream and are oxidized by free radicals in the subendothelium.
oxidized LDL induces formation of adhesion molecules on the cell surface of the endothelium;
monocytes are ‘captured’ from the bloodstream by adhesion molecules and enter the subendothelial space;
monocytes penetrate the intima and differentiate into macrophages which bind and absorb oxidized LDL via the non-regulated scavenger receptor.
As macrophages accumulate cholesterol esters (CEs) they transform into foam cells.

2. Lipid core constitution LDL oxidation
Figure 23 Atherogenic lipoproteins (LDL or other apo B-containing lipoproteins) penetrate the intima. This renders them susceptible to oxidation – the auto-oxidation lipid cycle. Oxidized LDL contains modified apo B which is not recognized by the normal receptors. Instead, it is recognized by the non-regulated scavenger receptor on the activated macrophage.

3. Parietal vascular inflammation The activated macrophage produces inflammatory cytokines
Figure 24 Oxidized LDL contains large amounts of cholesterol ester (CE). When macrophages are full of CE they secrete cytokines (IL-6, CRP, TNFa) which, in turn, induce vascular inflammation, cell recruitment, and weakening of the fibrous cap.

4. Parietal vascular inflammation NFkB action in the inflammation process
Figure 25 NFkB (a nuclear receptor) plays a major role in inflammation. After internalization and activation within the cell nucleus, NFkB activates genes responsible for synthesis of inflammation factors (IL-6, COX-2, TNFa, ICAM, VCAM). NFkB is, in turn, activated by cytokines, prostaglandins and leukotrienes.