Physical chemistry of the lipids of human atherosclerotic lesions. Demonstration of a lesion intermediate between fatty streaks and advanced plaques.

Abstract

A B S T R A C T 95 individual human atherosclerotic lesions from 26 persons were classified into three groups under the dissecting microscope: fatty streaks, fibrous plaques, and gruel (atheromatous) plaques. Each lesion was isolated by microdissection, its lipid composition determined by chromatography, and the physical states of the lipids identified by polarizing microscopy and in some cases by X-ray diffraction. The composition of each lesion was plotted on the in vitro phase diagram of the major lipids of plaques: cholesterol, cholesterol ester, and phospholipid. The observed physical states were compared with those predicted by the location of the lipid composition on the phase diagram.The most severe lesions (gruel plaques) had an average lipid composition of cholesterol 31.5±1.9%, cholesterol ester 47.2±2.3%, and phospholipid 15.3±0.5%.Their compositions fell within the three-phase zone of the phase diagram, predicting the lipids to be separated into a cholesterol crystal phase, a cholesterol ester oily phase and a phospholipid liquid crystalline phase. In addition to the phospholipid liquid crystalline phase of membranes and myelin-like figures demonstrable by electron microscopy, polarizing microscopy revealed the other two predicted phases, isotropic cholesterol esterrich droplets and cholesterol crystals. X-ray diffraction studies verified the identity of the crystals as cholesterol monohydrate.Fibrous plaques also had an average lipid composition within the three-phase zone of the phase diagram. Polarizing microscopy revealed the presence of cholesterol monohydrate crystals and lipid droplets in all of these lesions; the droplets were predominately isotropic in 28 of the 31 fibrous plaques. Although these lesions had less free cholesterol and more cholesterol ester than gruel plaques, they were otherwise similar.Fatty streaks had compositions within both the twoand three-phase zones of the phase diagram. Compared with gruel plaques, the fatty streaks within the twophase zone, defined as "ordinary," had more cholesterol ester, less free cholesterol, a higher cholesteryl oleate/ cholesteryl linoleate ratio, a lower sphingomyelin/lecithin ratio, more anisotropic lipid droplets, and rare or no cholesterol crystals. Those lesions within the three-phase zone had many chemical and physical features intermediate between ordinary fatty streaks and gruel plaques. Moreover, 68% of these "intermediate" lesions had no cholesterol crystals by polarizing microscopy in spite of their compositions being within the three-phase zone, indicating the cholesterol ester oily phase or the phospholipid phase or both were supersaturated with cho-

Development of the smooth muscle foam cell: uptake of macrophage lipid inclusions.

“…As is illustrated in Fig. 1 C and D (1,25). An electron micrograph of rabbit smooth muscle cells exposed to inclusions for 24 hr (Fig.…”

“…The accumulation of cholesteryl ester inclusions within cells of the large vessels has been established as one of the early events in the development of atherosclerosis (1)(2)(3). This deposition leads to the formation of cholesteryl ester-loaded cells, which have been termed foam cells.…”

George Lyman Duff memorial lecture. Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry.

“…These lipids make up about 95% of the total lipids in a normal intima and atherom a s [13][14][15][16][17][18][19] T n e m j n o r lipjds present in small amounts include triacylglycerols, fatty acids, and lysophospholipids. 13 The mean percent lipid and the average lipid composition for newborn intima 10 and the macroscopically identifiable atherosclerotic lesions 13 are given in Table 1. Cholesterol esters are nearly absent in newborn intima but are a major part of lesions.…”

“…However, arterial lesions and other biologic deposits of cholesterol esters may also contain small amounts of triacylglycerols 13 which could partition into the cholesterol esters. The cholesterol ester phase of plaque also contains small amounts of free cholesterol (3% to 5%), and these contaminants lower the transition temperature.…”

Combinatorial pattern recognition receptor signaling alters the balance of life and death in macrophages

“…The UPR is activated in advanced murine and human atherosclerotic lesions (9)(10)(11), and these lesions are known to contain a number of UPR activators (e.g., oxidant stress and nitric oxide) and SRA ligands (e.g., oxidized lipoproteins and advanced glycosylation end products) (12)(13)(14). Moreover, subpopulations of macrophages in apoptotic-rich areas of lesions are filled with lipoprotein-derived free cholesterol (FC) (15)(16)(17)(18)(19). In this scenario, the modified lipoproteins engage the SRA, and the lipoprotein-derived FC activates the UPR, leading to macrophage apoptosis (8).…”