Physical factors that trigger cholesterol crystallization leading to plaque rupture

Atherosclerosis. 2009 Mar;203(1):89-96. doi: 10.1016/j.atherosclerosis.2008.06.027. Epub 2008 Jul 6.


Background: Triggers 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.

Methods: Graduated cylinders were filled with varying amount of cholesterol powder (1, 2 and 3g) and dissolved in corn oil at 37 degrees C. Change in volume expansion (DeltaVE) and time to crystallization were measured for each saturation. The same was repeated while varying temperature (22-44 degrees C); hydration (1-3ml H(2)O); 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.

Results: Increasing saturation raised both DeltaVE (3g: 0.53+/-0.1ml vs. 1g: 0.14+/-0.02ml and 2g: 0.3+/-0.1ml; p<0.0001; p<0.01) and rate of change over 3min (3g: 60% vs. 1g: 14%). Crystal morphology was the same seen with crystals perforating human plaques. Temperature drop increased DeltaVE (44 degrees C: 0.05+/-0.01ml vs. 22 degrees C: 0.5+/-0.07ml; p<0.0001) and initiated earlier crystallization. Hydration resulted in greater DeltaVE (3ml: 0.7+/-0.07 vs. 0ml: 0.1+/-0.05; p<0.001) with corresponding changes in cholesterol molecular structure. Rising pH was associated with increased DeltaVE (1.3+/-0.03ml vs. 0.1+/-0.02ml; p<0.001). Combined increase in saturation and temperature had greater DeltaVE than expected from the sum of each alone.

Conclusions: Physical 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / pathology
  • Atherosclerosis / pathology*
  • Cholesterol / metabolism*
  • Coronary Vessels / pathology
  • Coronary Vessels / ultrastructure
  • Crystallization
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Microscopy, Electron, Scanning
  • Middle Aged
  • Models, Statistical
  • Myocardial Infarction / metabolism*
  • Stroke / metabolism*
  • Temperature
  • X-Ray Diffraction


  • Cholesterol