期刊
EXPERIMENTAL AND MOLECULAR PATHOLOGY
卷 93, 期 2, 页码 220-226出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yexmp.2012.03.014
关键词
Foam cell; Atherosclerosis; Inflammation; Modified LDL; Cholesterol; Macrophage
类别
资金
- Australian Centre for HIV and Hepatitis Research
- National Institutes of Health of the United States [HL072942]
- German Academic Exchange Service (DAAD)
- NHMRC
Foam cells are a pathological feature present at all stages of atherosclerosis. Foam cells develop from monocytes that enter the nascent atheroma and subsequently ingest modified low density lipoproteins (LDL). The regulation of this process has previously been studied in vitro using cultured macrophage fed modified LDL We used our existing in vitro model of transendothelial migration (TEM) to study this process in a more physiologically relevant setting. In our model, monocytes undergo TEM across a primary endothelial monolayer into an underlying three-dimensional collagen matrix in the presence of 20% human serum. Foam cells were detected by Oil Red 0 staining for intracellular lipid droplets. We demonstrate that sub-endothelial monocytes can develop into foam cells within 48 h of TEM across TNF-alpha activated endothelium, in the absence of additional lipids. Our data indicate a role for both monocyte-endothelial interactions and soluble factors in the regulation of foam cell development including oxidation of LDL in situ from lipid present in culture medium following TNF-alpha stimulation of the endothelial cells. Our study provides a simple model for investigating foam cell development in vitro that mimics cell migration in vivo, and demonstrates the critical role of inflammation in regulating early atherogenic events. (C) 2012 Elsevier Inc. All rights reserved.
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