1. Arterial wall: structure and function
Figure 7 In order to understand AS, one must understand the structure and function of the artery.
The artery has three structural components:
adventitia (which carries blood and nerve supply to the artery itself);
media (comprised of smooth muscle, which controls vascular tone);
intima (a basement membrane covered by endothelium which regulates hemostasis, thrombosis, vascular tone and permeability).
The intima is the site of AS.

2. Different stages of atherosclerotic plaque development
Figure 8 There are six stages of development of AS:
Grades I – IV: accumulation of lipids, first intracellularly, then extracellularly;
Grade V: fibrosis around the lipid core forming an atherosclerotic plaque;
Grade VI: complicated plaque (rupture, clot or bleed) leading to a clinical event.

3. Vascular endothelium modification in atherosclerosis
Figure 9 During AS, the integrity of the endothelium is compromised which results in:
increased permeability, which facilitates the penetration of the intima by atherogenic lipoproteins;
increased adhesion, which facilitates migration of monocytes into the subendothelium;
diminished vasodilation, which compromises hemodynamic control.

4. Plaque formation 1 — Fatty streak
Figure 10 Monocytes penetrate the intima and are transformed into macrophages and eventually cholesterol-rich foam cells. These activated macrophages scavenge and ingest oxidized low-density lipoprotein (LDL) in the subendothelial space. The progressive accumulation of lipids (intra- and extracellular) forms the fatty streak.

5. Plaque formation 2 — Fibrous cap
Figure 11 The growing fatty streak eventually forms the lipid core, which becomes isolated by the progressive formation of a fibrous cap. The fibrous cap contains collagen, proteoglycans and activated smooth muscle cells. The sturdier the cap, the less likelihood there is of plaque rupture.

6. Plaque formation 3 — Lipid core
Figure 12 Further lipid accumulation in the lipid core results in cell death (apoptosis).

7. From plaque to thrombosis, key event: plaque rupture
Figure 13 The key event in transformation of a stable plaque to an unstable plaque is rupture, which results in either partial or complete occlusive thrombosis.