Does Cholesterol in the Lipid Core Leak Out?
No, cholesterol in the lipid core does not "leak out" or seep through an intact fibrous cap under normal circumstances; instead, it remains sequestered within the plaque until the cap ruptures or erodes, at which point the highly thrombogenic lipid core is suddenly exposed to circulating blood. 1
Mechanism of Lipid Core Containment
The lipid core is physically contained within the atherosclerotic plaque by the fibrous cap, which acts as a structural barrier separating the thrombogenic core contents from the arterial lumen. 1, 2
- The fibrous cap is composed primarily of type I collagen that can support high tensile stress without breaking under normal conditions. 1
- The lipid core forms a cellular mass within the collagen matrix of the plaque, not as a freely mobile liquid that can diffuse through tissue. 1
- Cholesterol exists in the core as cholesteryl esters with high concentrations of polyunsaturated fatty acids, forming a semi-liquid to solid mass depending on local conditions. 1, 2
What Actually Happens: Rupture, Not Leakage
The critical pathophysiologic event is plaque disruption through rupture or erosion, not gradual leakage:
Active Rupture Mechanisms
- Macrophage-derived metalloproteinases actively degrade the collagen scaffold of the fibrous cap, weakening its structural integrity. 1, 2
- Smooth muscle cell apoptosis reduces the cap's cellular support, making it more vulnerable to mechanical stress. 1, 2
- The dynamic equilibrium between collagen synthesis and degradation shifts toward degradation in vulnerable plaques. 1, 2
Passive Rupture Mechanisms
- Physical forces concentrate at the thinnest portion of the fibrous cap, typically at the junction between the plaque and adjacent normal arterial wall. 1, 2
- Circumferential wall stress depends on plaque location, size, and lipid core composition, with vulnerable plaques having large lipid cores and thin caps (<65-70 micrometers). 1, 2
Cholesterol Crystal Formation Can Cause Traumatic Rupture
- Cholesterol crystallization from liquid to solid state causes volume expansion that can physically tear the plaque cap from within. 3, 4
- Cholesterol crystals have been observed perforating the cap and intimal surface in plaques from patients who died with acute coronary syndrome. 3
- Rapid transition of metastable cholesterol crystals into large flat plate crystals within lipid-rich plaques can lead to traumatic injury by expanding the necrotic core. 5
Thrombotic Consequences of Exposure
When the cap ruptures (not leaks), the consequences are immediate and catastrophic:
- The lipid-rich core is highly thrombogenic with greater tissue factor concentration than other plaque components. 1, 2
- Tissue factor activity correlates strongly with macrophage presence at the rupture site. 1, 2
- When rupture occurs, thrombus propagates into deeper plaque layers down to the lipid core, potentially causing subtotal or total vessel occlusion. 1, 2
- Thrombus formation leads to rapid changes in stenosis severity, resulting in acute coronary syndromes. 1, 2
Common Pitfall to Avoid
Do not conceptualize atherosclerotic plaque progression as a gradual "oozing" or leakage of cholesterol through an intact cap. 1 The pathophysiology is fundamentally different: the lipid core remains contained until a discrete rupture or erosion event suddenly exposes thrombogenic material to blood, triggering acute thrombosis. 1, 2, 6
Clinical Implications
- Plaque rupture is unpredictable and sudden, not a gradual process of lipid seepage. 1
- Vulnerable plaques are characterized by large lipid cores, thin fibrous caps (<65-70 µm), high macrophage density, and low smooth muscle cell content—all features that predispose to rupture, not leakage. 1, 2
- Current imaging cannot reliably identify which plaques will rupture, as the critical fibrous cap thickness (70 µm) is 10 times beyond the resolution of MDCT (750 µm) and MRI (500-780 µm). 1, 7