Development of the Lipid-Rich Core in Human Atherosclerosis

Abstract

T he core region of atherosclerotic plaques is char- acterized by profuse lipid deposition and disappearance of cells and fibrous tissue elements.Enlargement of the core, unless impeded or contained, leads to plaque rupture and consequently arterial thrombosis.'" 3 Although the core has been examined most commonly in advanced atherosclerosis, recent studies have shown that it originates early in lesion development-at the stage of transition from fatty streak to fibrous plaque.45 Thus, the development of the atherosclerotic core spans the entire period of fibrous plaque evolution, emphasizing the need to understand the cellular and extracellular processes that underlie core development.This is the first review to focus specifically on the origins and characteristics of the abundant extracellular lipid deposits and associated proteins found in the atherosclerotic core.A complete understanding of core development must include topics such as cytotoxicity, calcification, neovascularization, matrix degradation, and plaque rupture, but space permits only minimal coverage here, and the reader is referred to other articles and reviews. 2 -3ft -14 Core Initiation Is an Early Event in Lesion DevelopmentCore initiation may be recognized by the onset of typical lipid deposits, the partial disappearance of cells, or both.Early manifestations are difficult to discern in routine, paraffin-embedded tissue, primarily because of solvent extraction of the characteristic lipid deposits.Nevertheless, Restrepo and Tracy 15 noted foci of necrosis in human aortic fatty streaks and associated the presence of such foci with the subsequent development of fibrous plaques.Katz et al 16 examined tissue minces of arterial intima without solvents and found cholesterol crystals in a subset of flat human aortic lesions with the surface appearance of fatty streaks.The lesions that contained cholesterol crystals also showed relatively high levels of free cholesterol by chemical analysis.Epoxy-embedded tissue affords greatly improved recognition of the tissue clefts vacated by solvent extraction