Regulation of apolipoprotein E production in macrophages (review).
Apolipoprotein E (apo E), a 34 kDa component of lipoproteins produced by the liver and in circulating macrophages, plays a critical role in the reverse transport of cholesterol to the liver via the circulation. Cholesterol-rich macrophages (macrophage foam cells) are a major cell type in human atherosclerotic lesions. Apo E deficiency in mice leads to the formation of atherosclerotic lesions. Conversely, macrophage-specific expression of apo E in these deficient mice can reduce the extent of atherosclerosis. These observations, together with the anti-inflammatory and anti-proliferative properties of Apo E, demonstrate an atheroprotective role for the apolipoprotein. Agents that regulate macrophage metabolism are also able to modulate apo E expression. Sterol loading, for example, enhances apo E synthesis and secretion. Additionally, exposure of macrophage foam cells to cholesterol acceptors such as apo A-1, the protein component of high density lipoprotein, further enhance apo E secretion. Cytokines can have a negative regulatory effect on apo E production in macrophages. Apo E expression is controlled at the transcriptional, post-transcriptional and post-translational level. Here, we review the cellular and molecular mechanisms modulating apo E synthesis and secretion in macrophages.
Larkin
L
L
Cell Biology Group, The Heart Research Institute, Camperdown, Sydney, Australia.
Khachigian
L M
LM
Jessup
W
W
D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis*; D001161:Arteriosclerosis / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*
D001057:Apolipoproteins E