Mechanism of necrotic core expansion

Putative mechanism(s) of necrotic core expansion in human coronary plaques. A to C illustrate the concept of early, late, and hemorrhagic necrosis, respectively. A lipid pool rich in proteoglycans and CD68-positive macrophages characterizes the early fibroatheroma; there is a general absence of smooth muscle cells.
(A) Infiltrating macrophages capable of engulfing apoptotic bodies (ABs) are clearly recognized within the necrotic core (NC).
(B) As the lesion advances, late necrosis is represented by increased macrophage death and cell lysis and apparent loss of extracellular matrix. In this case, free apoptotic bodies are commonly seen, possibly indicating the defective clearance (efferocytosis) by resident macrophages.
(C) In the third example, hemorrhage may promote the relatively rapid expansion of necrotic core where erythrocytes membranes provide free cholesterol (Free-Chol, arrow), which may cause secondary inflammation. Resident macrophages are capable of removing hemoglobin/haptoglobin complexes via the CD163 receptor, although the efficiency of this mechanism is likely compromised as well.