Physical factors that trigger cholesterol crystallization leading to plaque rupture

Research output: Contribution to journalArticle

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Abstract

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 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. Results: Increasing 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. 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.

LanguageEnglish (US)
Pages89-96
Number of pages8
JournalAtherosclerosis
Volume203
Issue number1
DOIs
StatePublished - Mar 2009

Profile

Crystallization
Rupture
Cholesterol
Temperature
Molecular Structure
Corn Oil
Electron Scanning Microscopy
Powders
X-Rays

Keywords

  • Cholesterol crystals
  • Myocardial infarction
  • Plaque rupture
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Physical factors that trigger cholesterol crystallization leading to plaque rupture. / Vedre, Ameeth; Pathak, Dorothy R.; Crimp, Martin; Lum, Chee; Koochesfahani, Manoochehr; Abela, George S.

In: Atherosclerosis, Vol. 203, No. 1, 03.2009, p. 89-96.

Research output: Contribution to journalArticle

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title = "Physical factors that trigger cholesterol crystallization leading to plaque rupture",
abstract = "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 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. Results: Increasing 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. 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.",
keywords = "Cholesterol crystals, Myocardial infarction, Plaque rupture, Stroke",
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AU - Vedre,Ameeth

AU - Pathak,Dorothy R.

AU - Crimp,Martin

AU - Lum,Chee

AU - Koochesfahani,Manoochehr

AU - Abela,George S.

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N2 - 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 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. Results: Increasing 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. 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.

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