Cholesterol crystals in the pathogenesis of atherosclerosis

The presence of cholesterol crystals (CCs) in tissues was first described more than 100 years ago. CCs have a pathogenic role in various cardiovascular diseases, including myocardial infarction, aortic aneurysm and, most prominently, atherosclerosis. Although the underlying mechanisms and signalling pathways involved in CC formation are incompletely understood, numerous studies have highlighted the existence of CCs at various stages of atheroma progression. In this Review, we summarize the mechanisms underlying CC formation and the role of CCs in cardiovascular disease. In particular, we explore the established links between lipid metabolism across various cell types and the formation of CCs, with a focus on CC occurrence in the vasculature. We also discuss CC-induced inflammation as one of the pathogenic features of CCs in the atheroma. Finally, we summarize the therapeutic strategies aimed at reducing CC-mediated atherosclerotic burden, including approaches to inhibit CC formation in the vasculature or to mitigate the inflammatory response triggered by CCs. Addressing CC formation might emerge as a crucial component in our broader efforts to combat cardiovascular disease.