1.In vitro model of atherosclerosis using coculture of arterial wall cells and macrophage.
Youichiro WADA ; Akira SUGIYAMA ; Takahide KOHRO ; Mika KOBAYASHI ; Motohiro TAKEYA ; Makoto NAITO ; Tatsuhiko KODAMA
Yonsei Medical Journal 2000;41(6):740-755
In order to determine the precise mechanism of the interactions between different types of cells, which are common phenomena in tissues and organs, the importance of coculture techniques are becoming increasingly important. In the area of cardiology, artificial arteries have been developed, based on the understanding of physiological communication of the arterial smooth muscle cells (SMC), endothelial cells (EC), and the extracellular matrix (ECM). In the study of atherosclerosis, the modification of low-density lipoprotein (LDL), which result in the recruitment and accumulation of white blood cells, especially, monocytes/macrophages, and foam cell formation, are hypothesized. Although there are well known animal models, an in vitro model of atherogenesis with a precisely known atherogenesis mechanism has not yet been developed. In this paper, an arterial wall reconstruction model using rabbit primary cultivated aortic SMCs and ECs, was shown. In addition, human peripheral monocytes were used and the transmigration of monocytes was observed by scanning electron and laser confocal microscopy. Monocyte differentiation into macrophages was shown by immunohistochemistry and comprehensive gene expression analysis. With the modified form of LDL, the macrophages were observed to accumulate lipids with a foamy appearance and differentiate into the foam cells in the ECM between the ECs and SMCs in the area of our coculture model.
Animal
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Aorta/physiology*
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Aorta/cytology*
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Arteriosclerosis/etiology*
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Cell Differentiation/physiology
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Cell Movement
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Coculture
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Endothelium, Vascular/physiology
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Endothelium, Vascular/cytology
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Extracellular Matrix/metabolism
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Foam Cells/ultrastructure
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Foam Cells/cytology
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Macrophages/physiology*
;
Macrophages/cytology
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Male
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Microscopy, Confocal
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Microscopy, Electron
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Microscopy, Electron, Scanning
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Monocytes/ultrastructure
;
Monocytes/physiology
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Muscle, Smooth, Vascular/physiology
;
Muscle, Smooth, Vascular/cytology
;
Myosin/metabolism
;
Protein Isoforms/metabolism
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Rabbits