What is Atherosclerosis?

• Atherosclerosis is a lipoprotein-driven disease that leads to the formation of plaque inside arteries.
• It affects specific areas of arteries and is considered a multivocal disease, meaning it impacts the entire vascular system.
• The plaques, also known as atheroma, are made up of lipids, inflammatory cells, smooth muscle cells, and connective tissue.

Key Concepts in Atherosclerosis

• Plaque burden refers to the extent of atherosclerosis in the arteries.
• Plaque activity is a broad term that could encompass various processes involved in plaque progression.
• Plaque vulnerability indicates the short-term risk of a plaque leading to symptomatic thrombosis.

How Atherosclerotic Plaques Form

1. Lipoprotein Accumulation: Low-density lipoproteins (LDL) accumulate in artery walls.
2. Inflammatory Response: LDL build-up triggers inflammation, bringing white blood cells (e.g., macrophages) to the artery walls.
3. Foam Cell Formation: Macrophages absorb lipids, turning into foam cells.
4. Fatty Streak Formation: These foam cells gather in the artery walls, creating fatty streaks.
5. Necrotic Core Development: As the plaque grows, cells in the core die, forming a necrotic core.
6. Fibrous Cap Formation: Smooth muscle cells generate a fibrous cap over the necrotic core, stabilising the plaque.
7. Plaque Progression: Plaques harden due to calcium deposits, narrowing the arteries further.

Types of Atherosclerotic Lesions

• Adaptive Intimal Thickening: Early-stage lesion with smooth muscle build-up.
• Intimal Xanthoma: Foam cells accumulate in the intima layer.
• Pathological Intimal Thickening: Lipid pools form in the artery wall without necrosis.
• Fibroatheroma: Advanced lesion with a necrotic core and fibrous cap.
  • Thin-Cap Fibro atheroma (TCFA): A subtype more prone to rupture due to a thin fibrous cap.
• Fibrocalcific Plaque: Hardened plaque with calcium build-up.

What Happens When Plaques Rupture?

• Plaque Rupture: The fibrous cap of a plaque, especially in TCFAs, can rupture, exposing the necrotic core to the bloodstream.
• Thrombosis: The necrotic core activates tissue factor, leading to clot formation.
• Acute Coronary Syndromes: If a clot blocks a coronary artery, it can result in unstable angina, heart attack, or sudden death.

Factors Influencing Plaque Stability

• Necrotic Core Size and Composition: Larger lipid-rich necrotic cores increase the risk of rupture.
• Fibrous Cap Thickness: Thin caps with fewer smooth muscle cells and more macrophages are prone to rupture.
• Inflammation: Ongoing inflammation weakens the fibrous cap.
• Neovascularisation: New blood vessels in the plaque can cause internal bleeding, increasing rupture risk.
• Mechanical Stress: Hemodynamic forces, like shear stress, can affect plaque stability.

Additional Considerations

• Most current knowledge about atherosclerosis comes from autopsy studies and animal models, especially those with extreme hypercholesterolemia.
• More research is needed to understand how other risk factors beyond LDL contribute to plaque formation.

References

1. Libby, P. (2014). Inflammation in atherosclerosis. Circulation Research, 114(7), 948-963.
2. Braunwald, E. (2008). The path to an understanding of atherosclerosis. The American Journal of Medicine, 121(10), S2-S6.
3. Hansson, G. K., & Hermansson, A. (2014). The immune system in atherosclerosis. Journal of Internal Medicine, 275(4), 391-403.
4. ScienceDirect. (n.d.). Mechanism of Atherosclerosis. Retrieved from https://www.sciencedirect.com/topics/medicine-and-dentistry/mechanism-of-atherosclerosis