2017
DOI: 10.1186/s12944-017-0629-9
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Quantification of sterol-specific response in human macrophages using automated imaged-based analysis

Abstract: BackgroundThe transformation of normal macrophage cells into lipid-laden foam cells is an important step in the progression of atherosclerosis. One major contributor to foam cell formation in vivo is the intracellular accumulation of cholesterol.MethodsHere, we report the effects of various combinations of low-density lipoprotein, sterols, lipids and other factors on human macrophages, using an automated image analysis program to quantitatively compare single cell properties, such as cell size and lipid conten… Show more

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Cited by 4 publications
(4 citation statements)
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References 58 publications
(69 reference statements)
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“…Thus, if our model is correct, the effects of Upc2 mutants on pyroptosis are readily explained by alterations in the levels of overall cellular ergosterol. Second, a head-to-head comparison of the toxicity of sterols toward macrophages indicates that ergosterol is more toxic to macrophages than cholesterol ( 46 ). Although the mechanism of this toxicity was not characterized further, it is interesting to consider the fact that ergosterol does not activate liver X receptor (LXR), a key regulator of sterol efflux in liver and macrophage cells ( 47 ).…”
Section: Discussionmentioning
confidence: 99%
“…Thus, if our model is correct, the effects of Upc2 mutants on pyroptosis are readily explained by alterations in the levels of overall cellular ergosterol. Second, a head-to-head comparison of the toxicity of sterols toward macrophages indicates that ergosterol is more toxic to macrophages than cholesterol ( 46 ). Although the mechanism of this toxicity was not characterized further, it is interesting to consider the fact that ergosterol does not activate liver X receptor (LXR), a key regulator of sterol efflux in liver and macrophage cells ( 47 ).…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, these platforms must be thoroughly characterized, and a profound understanding of individual contributions of the cells involved in atherosclerosis development must be reached before venturing to co-culture models. Most atherosclerosis studies are carried on 2D tissue culture plates [16]. While meaningful contributions have been made towards 3D modeling atherosclerosis in vitro, most studies have focused on co-culture of endothelial cells (ECs), smooth muscle cells (SMCs), and monocytes, in either physiological [18] or synthetic [20] scaffolds, while detailed individual contributions of macrophages still remain unclear.…”
Section: Resultsmentioning
confidence: 99%
“…Animal models have provided abundant information for atherosclerosis research, however, to understand atherosclerosis healing mechanistically, relevant in vitro models are a must. Models of atherosclerosis have progressed from simple 2D culture to 3D multi-cellular cultures [ 16 , 17 ], the latter a better representation considering the dimensionality of the disease and anatomical features involved. To mimic in vivo-like conditions, in vitro models have encapsulated the relevant cells of interest within naturally-derived and polymer-based hydrogels.…”
Section: Introductionmentioning
confidence: 99%
“…These technological processes have enabled the development of fine structures that closely resemble those in vivo [19,20]. Furthermore, powerful computational techniques that allow the quantification of cellular behavior even at the single cell level are now being available and can be combined with microfluidic technology to provide a comprehensive description of cellular behavior under various stimuli [21,22,23].…”
Section: Introductionmentioning
confidence: 99%