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Cytotoxicity of oxidized low-density lipoprotein to mouse peritoneal macrophages: an ultrastructural study
V C Reid1, M J Mitchinson, J N Skepper
1Department of Pathology, University of Cambridge, U.K.
Abstract:
Mouse peritoneal macrophages (MPM) were incubated in culture medium containing low-density lipoprotein (LDL), oxidized LDL (oxLDL), or as controls, for 24 h. Scanning electron microscopy of MPM exposed to oxLDL showed loss of membrane ruffles and extensive plasmalemmal 'blebbing'. Transmission electron microscopy showed changes in up to 50 per cent of the cells, including vacuolation of the rough endoplasmic reticulum and reorganization of heterochromatin in the nuclei, characteristic of apoptosis. These changes were not seen in controls, nor in macrophages exposed to native LDL. Electron-dense crystals were found in the cytoplasm of 1 in 50 of cells exposed to oxLDL. These were found to have a high content of calcium and phosphorus. It is proposed that oxLDL is capable of inducing apoptosis, which might explain the origin of the necrotic base of advanced atherosclerotic plaques.
Insights
Oxidized low-density lipoprotein (oxLDL) induces apoptosis in mouse peritoneal macrophages (MPM). This cellular damage, characterized by blebbing and nuclear changes, may contribute to atherosclerotic plaque development.
Area of Science:
- Cell Biology
- Cardiovascular Research
- Pathology
Background:
- Atherosclerosis is a complex disease involving lipid accumulation and inflammation in artery walls.
- Macrophage dysfunction plays a critical role in the pathogenesis of atherosclerotic plaques.
- The precise mechanisms by which modified lipids influence macrophage behavior are under investigation.
Purpose of the Study:
- To investigate the effects of oxidized low-density lipoprotein (oxLDL) on mouse peritoneal macrophages (MPM).
- To determine if oxLDL induces programmed cell death (apoptosis) in macrophages.
- To explore the potential link between oxLDL-induced macrophage apoptosis and the development of atherosclerotic plaques.
Main Methods:
- Mouse peritoneal macrophages (MPM) were cultured with native low-density lipoprotein (LDL) or oxidized LDL (oxLDL).
- Scanning and transmission electron microscopy were used to examine cellular morphology.
- Cellular changes indicative of apoptosis, including nuclear and endoplasmic reticulum alterations, were assessed.
- Elemental analysis was performed on intracellular crystals.
Main Results:
- Exposure to oxLDL caused significant morphological changes in MPM, including membrane blebbing and loss of ruffles.
- Transmission electron microscopy revealed apoptotic features in up to 50% of oxLDL-treated cells.
- Native LDL did not induce these changes.
- Electron-dense crystals containing calcium and phosphorus were observed in the cytoplasm of some oxLDL-exposed cells.
Conclusions:
- Oxidized LDL (oxLDL) is capable of inducing apoptosis in mouse peritoneal macrophages (MPM).
- These findings suggest a potential mechanism for the formation of the necrotic core in advanced atherosclerotic plaques.
- Oxidized LDL-induced macrophage apoptosis may be a key factor in the progression of atherosclerosis.