Definitions

• Arteriosclerosis: an umbrella term to describe arterial wall thickening (hardening) and elasticity loss with variable pathogenesis
• Atherosclerosis
  • Most common type of arteriosclerosis
  • Multifactorial inflammatory disease of the intima, manifesting at points of hemodynamic shear stress
  • Characterized by a build-up of cholesterol plaques in the tunica intima
  • Affects elastic arteries and large/medium-sized muscular arteries
• Monckeberg arteriosclerosis
  • A form of arteriosclerosis characterized by dystrophic calcification of the tunica media and internal elastic lamina
  • There is no blood flow obstruction.
    • The intimal layer of the artery is not involved.
  • Mainly affects medium-sized arteries
  • Causes: diabetes mellitus and/or progressive kidney disease
  • X-ray: pipestem appearance
• Arteriolosclerosis: the thickening and loss of elasticity of the small arteries and arterioles
  • Hyaline arteriolosclerosis
    • Deposition of proteins below the endothelium due to plasma protein leakage
    • H&E: pink amorphous deposits (hyaline) within the arteriolar walls
    • Causes: chronic essential hypertension, diabetes mellitus, and normal aging
  • Hyperplastic arteriolosclerosis
    • Proliferation of subendothelial smooth muscle cells in response to very high blood pressure
    • H&E: “onion-skin” appearance of the arteriole
    • Cause: malignant hypertension

Pathogenesis of atherosclerosis

1. Chronic stress on the endothelium (e.g., due to arterial hypertension and turbulence)
2. Endothelial cell dysfunction, which leads to:
   • Invasion of inflammatory cells (mainly monocytes and lymphocytes) through the disrupted endothelial barrier
   • Adhesion of platelets to the damaged vessel wall → platelet release of inflammatory mediators (e.g., cytokines) and platelet-derived growth factor (PDGF)
   • PDGF stimulates the migration and proliferation of smooth muscle cells (SMCs) in the tunica intima and mediates the differentiation of fibroblasts into myofibroblasts
3. Inflammation of the vessel wall
4. Macrophages and SMCs ingest cholesterol from oxidized LDL and transform into foam cells (macrophages filled with lipid droplets).
5. Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).
6. Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) deposition → development of a fibrous plaque (atheroma)
   • Macrophages, smooth muscle cells, lymphocytes, and extracellular matrix form a fibrous cap, which covers a necrotic center, consisting of foam cells, free cholesterol crystals, and cellular debris.
7. Inflammatory cells in the atheroma (e.g., macrophages) secrete matrix metalloproteinases → weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap
8. Calcification of the intima (the amount and pattern of calcification affect the risk of complications)
9. Plaque rupture → exposure of thrombogenic material (e.g., collagen) → thrombus formation with vascular occlusion or spreading of thrombogenic material