Atherosclerosis Overview and Risk Factors

Atherosclerosis

• Atherosclerosis is a type of arteriosclerosis, hardening of the arteries.
• The term comes from Greek words: atheros ("gruel" or "paste") and sclerosis ("hardness").
• It involves the formation of fibro fatty lesions in the inner lining (intima) of large and medium-sized arteries.
• Affected arteries include the aorta and its branches, coronary arteries, and vessels supplying the brain.

Atherosclerosis: Objective

• The objective is to describe the etiology (cause) and pathogenesis (development) of atherosclerosis.

Atherosclerosis: Etiology and Risk Factors

• Modifiable:
  • Hypercholesterolemia (high cholesterol) is a major risk factor.
• Non-modifiable:
  • Increasing age (men ≥ 45 years, women ≥ 55 years)
  • History of premature coronary heart disease (CHD)
  • Male sex
• Traditional Cardiovascular Risk Factors:
  • Cigarette smoking
  • High LDL (low-density lipoprotein) levels
  • Obesity and visceral fat
  • Hypertension (increases incidence by two-fold)
  • Type 2 diabetes mellitus (increases incidence by two-fold)
• Non-traditional Cardiovascular Risk Factors:
  • C-reactive protein levels (increased in vascular disease)
  • Serum homocysteine levels
  • Serum lipoprotein levels
  • Infectious agents: Chlamydia pneumoniae, Herpes virus, Cytomegalo virus (increases risk of vascular disease).

Atherosclerosis: Pathogenesis

• Atherosclerosis develops in stages. Clinical manifestations (symptoms) often take 20-40 years to become evident.
• Three types of lesions: fatty streaks, fibrous atheromatous plaque, and complicated lesions.
• Later two are responsible for clinically significant manifestations of the disease.

The Fatty Streaks

• Thin, yellow, flat discolorations in the inner lining
• Progressively enlarge by becoming thicker and slightly elevated.

The Fibrous Atheromatous Plaque

• Accumulation of intracellular and extracellular lipids
• Proliferation of vascular smooth muscle cells
• Formation of scar tissue

The Complicated Lesion

• Contains hemorrhage, ulceration, and scar tissue deposits.

Atherosclerosis: Pathogenesis – Development

• Endothelial cell injury (1):

  • Endothelium (inner lining) usually protects sub-endothelial layers from blood cells.
  • Smoking, elevated LDL, immune mechanisms, and mechanical stress (from hypertension) can cause damage and/or adhesion of monocytes and platelets.

• Migration of inflammatory cells (2):

  • Endothelial cells express adhesion molecules that bind monocytes and other inflammatory cells.
  • Monocytes migrate, become macrophages, and engulf lipoproteins (mostly LDL)

• SMC Proliferation and Lipid Deposition (3):

  • Macrophage activation releases toxic oxygen species that oxidize LDL. Oxidized LDL ingested to become foam cells.
  • Smooth muscle cells (SMCs) migrate and proliferate. Extracellular matrix (ECM) is elaborated.

• Development of the atheromatous plaque with a lipid core (4):

  • Plaques include smooth muscle cells, macrophages, other leukocytes, ECM (collagen and elastic fibers), intracellular & extracellular lipids.
  • Superficial fibrous cap composed of SMCs and dense ECM.
  • Cellular area (the shoulder) beneath the fibrous cap with macrophages, SMCs and lymphocytes.
  • Inner core made of lipid-laden foam cells and fatty debris.
  • Rupture, ulceration, erosion can cause hemorrhage or thrombosis (blood clot) in the vessel.

Atherosclerosis: Diagram of Normal and Plaque-Obstructed Artery

• Diagram shows a normal artery versus an artery with plaque build-up, which narrows the artery lumen.