Chronic Inflammatory disease of large & medium sized arteries due to endothelial injury. characterized by intimal lipid deposit, inflammation & fibrosis (atheroma / plaque)

unknown cause. Starts at bifurcations. Endothelial injury causes activation of monocytes and promote adhesion and migration into intima. development into intimal macrophage with scavenger receptors encourages uptake of LDL. LDL accumulated in macrophage, resulting in ‘foam cell’. excess LDL accumulation results in necrosis, releasing inflammatory mediators (IFN-gamma, TFN-alpha, IL-1, IL-6). released cholesterol forms crystals visible under microscope.

Macrophage activation

• M1 ‘classic’ pathway

• M2 ‘alternate’ pathway

• more healing less inflammation → stable plaque (90%)

• more inflammation less healing → unstable plaque (10%)

Stages of development

1. endothelial injury
2. LDL entry and oxidisation in intima
3. fatty/soft plaque - SMC proliferation and scarring
4. plaque change - Ulceration, thrombosis/thromboembolism, ACS

Clinical presentations

chronic obstruction (stable): IHD, PVD etc.

Thrombosis/embolism (unstable): ACS