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Prelesional events in atherogenesis: accumulation of extracellular cholesterol-rich liposomes in the arterial intima and cardiac valves of the hyperlipidemic rabbit
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The results show that an early prelesional ultrastructural change in lesion-prone aortic and valvular areas is the accumulation of extracellular phospholipid liposomes rich in unesterified cholesterol.Abstract:
Biochemical, physiologic, and ultrastructural modifications which appear in the aortic intima and atrioventricular valves before monocyte diapedesis and foam cell formation were investigated in rabbits fed a cholesterol-rich diet In the first 2 weeks of the diet, while plasma beta-VLDL cholesterol was increased up to 15-fold, the intima showed an enhanced uptake and deposition of dietary 3H-cholesterol, 125I-beta-VLDL, and the fluorescent beta-VLDL-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine conjugate beta-VLDL-gold complex perfused in situ was transcytosed across endothelium by plasmalemmal vesicles Concomitantly, within the intima, a progressive accumulation of extracellular densely packed uni- or multilamellar vesicles took place These commonly occurred in cell-free subendothelial spaces and were not associated with any sign of cytolysis In freeze-fracture preparations, these vesicles appeared as smooth surfaces, suggesting the absence of translamellar proteins Upon incubation with filipin, these extracellular liposomes (EL) displayed characteristic approximately 20 nm filipin-sterol complexes, revealing the presence of preparations unesterified cholesterol in the phospholipid lamellas EL deposition was paralleled by proliferation of basal lamina-like material, microfibrils, and proteoglycans, and continued to increase during foam cell formation For the entire period of our experiments, the endothelium was morphologically intact, and no platelet involvement was detected The results show that an early prelesional ultrastructural change in lesion-prone aortic and valvular areas is the accumulation of extracellular phospholipid liposomes rich in unesterified cholesterolread more
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TL;DR: The LDL Pathway is a Vehicle for Normal Human PhySIOLOGY and the PATHOGENESIS of ATHEROSCLEROSIS and its implications for normal human physiology and the pathogenesis of AtherOSCLerosis are discussed.
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Nile red: a selective fluorescent stain for intracellular lipid droplets.
TL;DR: The dye nile red, 9-diethylamino-5H- benzo[alpha]phenoxazine-5-one, is an excellent vital stain for the detection of intracellular lipid droplets by fluorescence microscopy and flow cytofluorometry and it exhibits properties of a near-ideal lysochrome.
Journal Article
The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions.
TL;DR: The results indicate that blood mononuclear cells associated with lesion formation in this model are, in fact, monocytes, which subsequently undergo transformation into macrophage foam cells in fatty streak lesions.