Physical factors that trigger cholesterol crystallization leading to plaque rupture

BackgroundTriggers of plaque rupture have been elusive. Recently it was demonstrated that cholesterol expands when transforming from a liquid to a crystal state, disrupting overlying plaque. This study examined the effect of physical conditions including saturation, temperature, hydration, pH on cholesterol crystallization.MethodsGraduated cylinders were filled with varying amount of cholesterol powder (1, 2 and 3 g) and dissolved in corn oil at 37 °C. Change in volume expansion (ΔVE) and time to crystallization were measured for each saturation. The same was repeated while varying temperature (22-44 °C); hydration (1-3 ml H2O); pH (5-8.4) and combination of saturation and temperature. Scanning electron microscopy was performed to evaluate crystal morphology and X-ray diffractometry to assess molecular structure of cholesterol.ResultsIncreasing saturation raised both ΔVE (3 g: 0.53 ± 0.1 ml vs. 1 g: 0.14 ± 0.02 ml and 2 g: 0.3 ± 0.1 ml; p < 0.0001; p < 0.01) and rate of change over 3 min (3 g: 60% vs. 1 g: 14%). Crystal morphology was the same seen with crystals perforating human plaques. Temperature drop increased ΔVE (44 °C: 0.05 ± 0.01 ml vs. 22 °C: 0.5 ± 0.07 ml; p < 0.0001) and initiated earlier crystallization. Hydration resulted in greater ΔVE (3 ml: 0.7 ± 0.07 vs. 0 ml: 0.1 ± 0.05; p < 0.001) with corresponding changes in cholesterol molecular structure. Rising pH was associated with increased ΔVE (1.3 ± 0.03 ml vs. 0.1 ± 0.02 ml; p < 0.001). Combined increase in saturation and temperature had greater ΔVE than expected from the sum of each alone.ConclusionsPhysical factors influenced both volume and rate of cholesterol crystallization. This suggests that local factors may play an important role in triggering plaque rupture. Combination of several factors may even be a more powerful trigger for acute cardiovascular events.