What are the microscopic findings of coronary atherosclerosis?

Microscopic Findings of Coronary Atherosclerosis

Coronary atherosclerosis is characterized microscopically by the accumulation of lipid-laden macrophages (foam cells) in the arterial intima, forming the earliest lesion known as a fatty streak, which progresses to complex plaques containing a lipid-rich necrotic core covered by a fibrous cap composed of smooth muscle cells and extracellular matrix.

Early Lesions: Fatty Streaks

• The earliest pathological abnormality is the fatty streak, consisting of lipid-filled macrophages (foam cells) accumulating within the arterial intima 1
• Circulating monocytes migrate into the subintimal space, transform into macrophages, and take up oxidized LDL particles to form foam cells 2
• LDL particles enter the arterial intima through passive molecular sieving and become trapped as they cannot penetrate the elastic laminas of the media 2
• Oxidized LDL must undergo modification before macrophages can take it up to form foam cells 2

Progressive Plaque Development

• With increasing age and continued lipid accumulation, macrophages and smooth muscle cells proliferate and migrate into the intima and media to form fibrous plaque lesions 1
• The mature atherosclerotic plaque consists of a large necrotic core formed by macrophage foam cells, overlaid by a fibrous cap composed of smooth muscle cells and extracellular matrix 3
• Macrophages are recognized as the hallmark cells of atherosclerotic plaques and are key players in the atherosclerotic process 1, 2

Vulnerable Plaque Characteristics

• Unstable or vulnerable plaques contain a soft, lipid-rich necrotic core covered by a thin, inflamed fibrous cap (thin-capped fibroatheroma) 1
• The thin fibrous cap measures approximately 70 µm in thickness 1
• These vulnerable plaques demonstrate intense accumulation of inflammatory cells, particularly macrophages, within the fibrous cap 1
• A scarce presence of smooth muscle cells characterizes the thin fibrous cap of vulnerable plaques 4
• Activated macrophages secrete metalloproteinases and other connective tissue enzymes that break down collagen, weakening the plaque cap and making it prone to rupture 2

Advanced and Complicated Lesions

• Advanced fibrous plaques are vulnerable to rupture, initiating a cascade of events leading to thrombus formation 1
• Plaque rupture or fissuring with subsequent thrombosis is what makes coronary atherosclerosis dangerous, potentially causing unstable angina, myocardial infarction, and sudden death 5
• Complications can occur when vascularization of the plaque leads to hemorrhage and swelling within the plaque, causing occlusion of the arterial lumen 1
• The risk of plaque disruption depends more on plaque composition (type) than on plaque size or stenosis severity 5

Cellular and Molecular Components

• Foam cells form when macrophages become filled with indigestible cholesterol droplets after taking up oxidized LDL 2
• Macrophages and foam cells in atherosclerotic plaques express lipoprotein lipase, which may stimulate foam cell formation from triglyceride-rich lipoproteins 2
• The atherosclerotic process involves an imbalanced lipid metabolism and a maladaptive immune response entailing chronic inflammation of the arterial wall 6

Artery-Specific Patterns

• Coronary atherosclerosis shows distinct patterns compared to other arteries, with lipid core plaques being more prevalent in individuals who die from coronary causes 7
• The left anterior descending coronary artery demonstrates the highest prevalence of atherosclerotic plaques 7