Extracellular lipid deposition in atherosclerosis

Abstract

Atherosclerotic lipid deposits found in the core region of fibrous plaques are almost entirely extracellular, but it is not known whether they are derived from necrosis of cells containing accumulated lipid or from direct extracellular lipid accumulation. New evidence pertaining to this question has been obtained through the use of recently developed techniques for preserving and staining lipids in electron microscopy, and through a detailed morphologic and chemical examination of human aortic fibrolipid lesions, which are progenitor lesions for fibrous plaques. The evidence favours a substantial role, perhaps a dominant role, for extracellular lipid accumulation in the formation of the fibrous plaque core region.

Effects of Intracellular Free Cholesterol Accumulation on Macrophage Viability

“…In summary, we have now demonstrated that many of the toxic events that are thought to occur within the atherosclerotic lesion, such as FC accumulation, 32 increased phospholipid synthesis, 38,50 -52 FC crystallization, 38,53,54 and apoptosis and necrosis, 39,55 can be reproduced in a model foam cell culture system. It is evident that in FC content in a foam cell can disturb the homeostatic balance and provoke toxic responses, such as necrosis and apoptosis.…”

Cysteine Protease Cathepsin F Is Expressed in Human Atherosclerotic Lesions, Is Secreted by Cultured Macrophages, and Modifies Low Density Lipoprotein Particles in Vitro

“…particle fusion, we next used a fusion assay based on 1 H NMR spectroscopy (49). In this assay, fusion of lipoprotein particles is detected by size-dependent chemical shifts in the 1 H NMR resonances of lipoprotein lipids. Fig.…”

“…extensively, as shown by the abundant generation of trichloroacetic acid-soluble apoB-100 fragments. The extensive degradation of apoB-100 in LDL by cathepsin F was accompanied by formation of aggregated and fused particles, as demonstrated by the increased turbidity of the samples, by the increased flotation of the particles in ultracentrifugation, by 1 H NMR spectrometry, and by electron microscopy. Interestingly, electron microscopy revealed that the proteolyzed particles resembled the lipid droplets found in the atherosclerotic human arterial intima (56 -58).…”

“…Initially, the droplets accumulate subendothelially (1). These droplets, which appear to be derived from low density lipoprotein (LDL) 1 particles, are entrapped by the arterial extracellular matrix, especially by its proteoglycans (2).…”

“…Initially, the droplets accumulate subendothelially (1). These droplets, which appear to be derived from low density lipoprotein (LDL) 1 particles, are entrapped by the arterial extracellular matrix, especially by its proteoglycans (2). In the intima, the proteoglycans form an organized tight network (3) that has the potential to bind apolipoprotein (apo) B-100-containing lipoproteins, notably LDL particles (4 -7).…”