PUBLICATION
Toll-like receptor-4 and lipoprotein accumulation in macrophages
- Authors
- Miller, Y.I., Choi, S.H., Fang, L., and Harkewicz, R.
- ID
- ZDB-PUB-100420-14
- Date
- 2009
- Source
- Trends in cardiovascular medicine 19(7): 227-232 (Review)
- Registered Authors
- Miller, Yury
- Keywords
- none
- MeSH Terms
-
- Animals
- Atherosclerosis/pathology
- Cholesterol Esters/metabolism
- Foam Cells/metabolism*
- Foam Cells/pathology
- Humans
- Lipoproteins, LDL/metabolism*
- Lipoproteins, LDL/physiology
- Macrophages/cytology
- Macrophages/metabolism*
- Macrophages/physiology
- Models, Biological
- Toll-Like Receptor 4/metabolism*
- Zebrafish
- PubMed
- 20382346 Full text @ Trends Cardiovasc. Med.
Citation
Miller, Y.I., Choi, S.H., Fang, L., and Harkewicz, R. (2009) Toll-like receptor-4 and lipoprotein accumulation in macrophages. Trends in cardiovascular medicine. 19(7):227-232.
Abstract
Excessive lipid accumulation in macrophages, also known as foam cell formation, is a key process during the development of atherosclerosis, leading to vascular inflammation and plaque growth. Recent studies have identified a new mechanism of macrophage lipid accumulation in which minimally oxidized low-density lipoprotein (mmLDL) and its active components, polyoxygenated cholesteryl ester hydroperoxides, are involved in endogenous activation of toll-like receptor-4 (TLR4), leading to recruitment of spleen tyrosine kinase (Syk), robust cytoskeletal rearrangements and macropinocytosis. In hyperlipidemic environments, mmLDL-induced, TLR4- and Syk-dependent macropinocytosis leads to substantial lipid accumulation in macrophages and monocytes, which may constitute an important mechanism of foam cell formation in atherosclerosis. A novel hypercholesterolemic zebrafish model of early stages of atherosclerosis was used to demonstrate that the TLR4 deficiency significantly reduces the in vivo rate of macrophage lipid accumulation in vascular lesions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping