How does plaque form in coronary arteries?

Plaque Formation in Coronary Arteries

Atherosclerotic plaque formation in coronary arteries is a complex inflammatory process involving lipid accumulation, oxidation, immune cell infiltration, and vascular remodeling that ultimately leads to the development of vulnerable plaques prone to rupture and thrombosis. 1

Initial Stages of Plaque Formation

• Lipid Accumulation: The process begins with the accumulation of low-density lipoprotein (LDL) cholesterol in the arterial intima 2
• Oxidative Modification: LDL particles become oxidized in the arterial wall, triggering an inflammatory response 2
• Endothelial Dysfunction: Damage to the endothelium (inner lining of arteries) occurs due to:
  • Hypertension
  • Smoking
  • Diabetes
  • Hyperlipidemia
  • Other cardiovascular risk factors 1, 3

Inflammatory Response and Plaque Progression

• Monocyte Recruitment: Oxidized LDL triggers the recruitment of monocytes from the bloodstream into the arterial wall 2
• Macrophage Transformation: Monocytes differentiate into macrophages that engulf oxidized LDL via scavenger receptors 2
• Foam Cell Formation: Macrophages become lipid-laden "foam cells" after ingesting large amounts of oxidized LDL 3
• Inflammatory Cascade:
  • T-lymphocytes and other immune cells are activated 1
  • Pro-inflammatory cytokines are released 4
  • C-reactive protein (CRP) and other inflammatory markers increase 4

Plaque Development and Vulnerability

• Lipid Core Formation: Foam cell death results in the accumulation of extracellular lipids and cellular debris, forming a lipid-rich necrotic core 3
• Smooth Muscle Cell Migration: Vascular smooth muscle cells migrate from the media to the intima, proliferate, and produce extracellular matrix proteins 3
• Fibrous Cap Formation: A fibrous cap composed of collagen and smooth muscle cells forms over the lipid core 2
• Vulnerable Plaque Characteristics: Plaques prone to rupture typically have:
  • Large lipid core
  • Low smooth muscle cell density
  • High macrophage density
  • Thin fibrous cap
  • Disorganized collagen
  • High tissue factor concentration 1

Plaque Disruption and Thrombosis

• Mechanisms of Plaque Disruption:

  • Active rupture: Secretion of proteolytic enzymes (metalloproteinases) by macrophages weakens the fibrous cap 1
  • Passive disruption: Physical forces act on the weakest point of the fibrous cap, typically at the junction with adjacent normal wall 1
  • Plaque erosion: Thrombus forms on the surface without cap rupture 5

• Thrombosis Formation:

  • The lipid-rich core exposed after plaque rupture is highly thrombogenic 1
  • Tissue factor in the plaque core activates the coagulation cascade 1
  • Platelets adhere to the disrupted plaque and aggregate 1
  • Thrombus formation can lead to partial or complete vessel occlusion 1

Key Insights About Plaque Vulnerability

• Stenosis Severity vs. Vulnerability: Approximately three-quarters of all infarct-related thrombi evolve over plaques causing only mild to moderate stenosis 1
• Inflammation as Key Driver: Inflammation plays a central role in plaque instability, making plaques vulnerable to rupture or erosion 6
• Dynamic Nature: The thrombotic response to plaque disruption is dynamic, with simultaneous thrombosis and clot lysis, often associated with vasospasm 1

Clinical Implications

• Plaque Composition vs. Stenosis: Plaque composition and vulnerability are more important predictors of future cardiovascular events than stenosis alone 7
• Therapeutic Targets:
  • Statins promote plaque regression, stabilization, and decreased inflammation 7
  • Antiplatelet therapy reduces risk of thrombotic events 7
  • Anti-inflammatory therapies are emerging as potential treatments 6

Understanding the complex process of plaque formation and disruption is essential for developing effective strategies to prevent and treat coronary artery disease and its potentially fatal complications.