Aernoud Fiolet

60 Chapter 2 Sudden changes in the physiochemical environment within the lipid pool of the plaque core, including changes in pH, cholesterol saturation, drop in temperature, 13 and hydration of cholesterol consequent to apoptosis or inflammatory injury related to necroptosis of macrophages, and other scavenger cells have the potential to trigger the rapid transition of previously quiescent metastable CCs into large rigid flat plate crystalline structures. This transition is associated with the release of latent elastic energy that can be forceful enough to cause the leading edge and sharp tips of larger extracellular CCs to pierce the vasavasorum causing intraplaque hemorrhage and cut through surrounding fibrous tissues causing plaque disruption and rupture (Fig. 3). 7,65 Figure 4. Schematic of multiple steps of crystal-related arterial injury. 1) Plaque rupturewith tethered edges of torn fibrous cap; 2) Released CCs traveling downstream disrupt endothelium and trigger vasospasm; 3) CCs lodged in muscle induce inflammatory injury. (bar = 200 μm light micrograph; bar = 50 μm scanning electron micrograph). Modified with permission. 66, 67, 68 CCs, cholesterol crystals. Unlike patients who died of noncardiac causes, in patients who died suddenly from myocardial infarction, the sites of plaque rupture in coronary arteries have been found to be studded with CCs perforating the fibrous cap and intima. 66 Histologically these ruptured plaques appear to have frayed cap edges consistent with “violent ripping and tearing” of the surrounding tissues as the underlying mechanism (Fig. 4). 7,66