Cell-mediated cholesterol crystal processing and clearance observed by 3D cryo-imaging in human atherosclerotic plaques

Abstract

AbstractAtherosclerosis is a pathology affecting the arteries, characterized by the buildup of plaques in the blood vessel walls. Atherosclerosis is the main cause of cardiovascular diseases, which constitute the leading cause of death in the world. Cholesterol crystals are the main components of the plaques, which actively participate in plaque growth and rupture and do not dissolve in aqueous environments. Employing novel cryo-scanning electron microscopy techniques, we examined human atherosclerotic plaques at high resolution, in 3D, and in close to native conditions. We show that cholesterol crystal clearance occurs in advanced human plaques through the activity of cells. We suggest that this occurs by enzymatic esterification of cholesterol to cholesteryl ester, which aggregates into intra- and extra-cellular pools. This discovery provides further understanding of the disease process in atherosclerosis, and may inspire new therapeutic approaches.