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Abundant expression of apoprotein E by macrophages in human and rabbit atherosclerotic lesions
M E Rosenfeld1, S Butler, V A Ord
1Division of Endocrinology and Metabolism, University of California at San Diego, La Jolla 92093-0682.
Abstract:
Previous studies have demonstrated the presence of apoprotein (apo) E protein and message in arterial lesions. To determine the source of the synthesized apoE, we performed simultaneous in situ hybridization and immunocytochemistry on human and rabbit atherosclerotic tissue. Studies of serial sections of aortic atherosclerotic lesions from humans and hypercholesterolemic New Zealand White rabbits and Watanabe heritable hyperlipidemic rabbits revealed a similar pattern of macrophage-specific apoE expression in the rabbit and human lesions. In early lesions of rabbit atherosclerotic tissue, in which many macrophages were present, there was abundant expression of apoE mRNA. Northern blot analyses of total mRNA obtained from arterial macrophage-derived foam cells, freshly isolated from ballooned, cholesterol-fed New Zealand White rabbits, demonstrated positive hybridization with an apoE-specific riboprobe. Western blot analyses of conditioned media from the isolated foam cells placed in culture for up to 24 hours demonstrated the presence of secreted apoE. These studies demonstrated that in atherosclerotic lesions, arterial wall macrophages synthesize and secrete apoE and probably account for most of the apoE synthesized in the atherosclerotic artery.
Insights
Arterial wall macrophages synthesize and secrete apoprotein E (apoE) within atherosclerotic lesions. This finding identifies macrophages as the primary source of apoE in arteries affected by atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Molecular Biology
Background:
- Apoprotein E (apoE) is present in arterial lesions.
- The cellular source of synthesized apoE in these lesions remains unclear.
Purpose of the Study:
- To determine the specific cell type responsible for apoE synthesis in atherosclerotic lesions.
- To investigate the role of macrophages in apoE production within the arterial wall.
Main Methods:
- Simultaneous in situ hybridization and immunocytochemistry on human and rabbit atherosclerotic tissues.
- Northern blot analysis of mRNA from isolated arterial macrophage-derived foam cells.
- Western blot analysis of conditioned media from cultured foam cells.
Main Results:
- Macrophage-specific expression of apoE was observed in both human and rabbit atherosclerotic lesions.
- Abundant apoE mRNA was detected in macrophages within early rabbit lesions.
- Isolated arterial foam cells synthesized and secreted apoE in vitro.
Conclusions:
- Arterial wall macrophages are the primary site of apoE synthesis in atherosclerotic lesions.
- Macrophages likely account for the majority of apoE produced within the atherosclerotic artery.
- These findings highlight the critical role of macrophages in apoE metabolism during atherosclerosis.