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JACC Cardiovasc Interv. 2011 May;4(5):521-9. doi: 10.1016/j.jcin.2011.02.010.

The impact of circulating cholesterol crystals on vasomotor function: implications for no-reflow phenomenon.

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College of Human Medicine, Department of Medicine, Division of Cardiology, Michigan State University, East Lansing, Michigan.



The purpose of this study was to determine if cholesterol crystals can injure the endothelial surface by their jagged edges altering vasoreactivity and contributing to no-reflow after intervention.


After plaque rupture, cholesterol crystals are released into the circulation and flow downstream contacting the arterial wall.


Both carotid arteries from 22 rabbits were placed in a dual perfusion chamber and challenged with norepinephrine followed by acetylcholine and nitroprusside. Arterial diameters were measured before and after exposure to cholesterol crystals or microspheres and compared with diameters of normal control arteries. Arteries were examined by light, confocal, atomic force and scanning electron microscopy.


Pre-exposure mean arterial diameter was 2.33 ± 0.27 mm. With baseline norepinephrine there was vasoconstriction of 0.82 ± 0.19 mm, 0.79 ± 0.18 mm, and 0.83 ± 0.16 mm in lumen diameter in the crystal, microsphere, and control groups, respectively. After cholesterol crystals or microspheres, vasoconstriction was significantly less for cholesterol crystals but not for microspheres (0.71 ± 0.28 mm and 0.81 ± 0.15 mm; p < 0.02 and p = 0.68). After acetylcholine in the same artery, there was significantly less dilation before versus after crystals (0.49 ± 0.24 mm vs. 0.38 ± 0.22 mm, p = 0.04) but not with microspheres or in the control group. There was no significant difference after nitroprusside in any group, suggesting endothelial injury. By scanning electron microscopy, cholesterol crystals were found embedded in the intima with endothelial cell tears whereas the microsphere treatment and control groups had minimal or no injury (93% vs. 31% vs. 14%; p < 0.01). By atomic force microscopy, surface roughness was significantly greater with cholesterol crystals compared with microspheres or in control arteries (p < 0.05).


Cholesterol crystals damaged the endothelium and reduced vasodilator response, potentially aggravating myocardial ischemia after interventions.

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