From the Guidelines
The central area of atherosclerosis described is a necrotic core, characterized by the presence of cholesterol crystals, foam cells, erythrocytes, and necrosis, which is a hallmark of advanced atherosclerosis. This region is formed due to the accumulation of lipids, inflammation, and cell death within the arterial wall, leading to the creation of a lipid-rich necrotic center within the plaque. The necrotic core is a signal-poor region with poorly delineated borders, as described by intravascular optical coherence tomography (IVOCT) studies 1. The presence of cholesterol crystals within the necrotic core is also supported by IVOCT evidence, which appears as thin, linear regions of high intensity, usually associated with a fibrous cap or necrotic core 1.
The formation of the necrotic core is a complex process involving the ingestion of oxidized LDL cholesterol by macrophages, which transform into foam cells and eventually die, releasing their contents 1. This process, combined with ongoing inflammation and the inability to clear cellular debris, leads to the formation of a lipid-rich necrotic center within the plaque. The characteristics of the necrotic core, including the presence of cholesterol crystals, foam cells, erythrocytes, and necrosis, distinguish it from other features such as hemorrhage, old hemorrhage, or thrombosis.
Key features of the necrotic core include:
- Presence of cholesterol crystals
- Foam cells
- Erythrocytes (red blood cells)
- Necrosis
- Signal-poor region with poorly delineated borders on IVOCT
- Association with a fibrous cap or necrotic core on IVOCT.
The clinical significance of the necrotic core lies in its role in the development of acute coronary syndromes, which are a major health problem and represent a large number of hospitalizations annually 1. The prognosis of acute coronary syndromes remains unfavorable, with a risk of death or non-fatal myocardial infarction complicating unstable angina ranging from 8% to 16% at 1-month follow-up 1.
From the Research
Characteristics of Atherosclerotic Plaques
- Atherosclerotic plaques are characterized by the accumulation of lipid-laden macrophage foam cells, cholesterol crystals, erythrocytes, and necrotic core in the intima of arterial walls 2, 3.
- The necrotic core is a region of dead cells and debris, which can be a source of inflammation and further damage to the plaque 2.
- The presence of cholesterol crystals, foam cells, and erythrocytes in the plaque can contribute to its instability and increase the risk of rupture or erosion 4, 5.
Inflammatory Mechanisms
- Atherosclerosis is an inflammatory disease, and the accumulation of lipids in the intima activates the endothelium to express leukocyte adhesion molecules and chemokines, promoting the recruitment of monocytes and T cells 4, 5.
- Monocytes differentiate into macrophages, which upregulate pattern recognition receptors, including scavenger receptors and Toll-like receptors, leading to the release of cytokines, proteases, and vasoactive molecules 4, 5.
- T cells in lesions recognize local antigens and mount T helper-1 responses with secretion of pro-inflammatory cytokines, contributing to local inflammation and growth of the plaque 4, 5.
Plaque Instability
- High-risk plaques have a large acellular lipid-rich necrotic core with an overlying thin fibrous cap infiltrated by inflammatory cells and diffuse calcification, making them more prone to rupture or erosion 2.
- The formation of new fragile and leaky vessels that invade the expanding intima can contribute to the enlargement of the necrotic core and increase the vulnerability of the plaque 2.
- Biomechanical, haemodynamic, and physical factors can also contribute to plaque destabilization, leading to the exposure of vascular structures or necrotic core components to the circulation and the subsequent formation of a thrombus 2.