The dissolution of cholesterol monohydrate crystals in atherosclerotic plaque lipids

Abstract

Uncomplicated human atherosclerotic plaques often contain large amounts of cholesterol esters and solid cholesterol monohydrate crystals. If such plaques are to regress the crystalline cholesterol would have to dissolve and be transported out of the arterial wall. Since cholesterol is quite insoluble in water, dissolution of plaque crystals might occur through lipids in the plaque, specifically, the cholesterol esters. As part of a study on feasibility of plaque reversal we have studied a specific step involving the dissolution of cholesterol monohydrate into cholesterol ester oil. With specific considerations of the composition and physical state of the cholesterol ester solvent, the size and form of cholesterol monohydrate crystals, the agitation rate, the temperature and the presence of water, we have found that cholesterol esters are an efficient solvent for cholesterol monohydrate crystals. The rate of dissolution was fast reaching 90% of saturation in 1 h. We conclude dissolution of cholesterol monohydrate into cholesterol ester oil is not a rate-limiting step in reversal of the atherosclerotic plaque. We suggest that transport of dissolved cholesterol from cholesterol ester oil may limit the removal. If transport of dissolved cholesterol could be enhanced, cholesterol monohydrate crystals could be rapidly dissolved and facilitate reversal of atherosclerotic lesions.