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Expression of apolipoprotein serum amyloid A mRNA in human atherosclerotic lesions and cultured vascular cells: implications for serum amyloid A function

Altered lipoprotein metabolism and vascular injury are considered to be major parts of the pathogenesis of atherosclerotic lesions. Serum amyloid A (SAA) is a family of acute-phase reactants found residing mainly on high density lipoproteins (HDL) in the circulation. Several functions for the SAAs h...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-04, Vol.91 (8), p.3186-3190
Main Authors: Meek, R.L, Uriel-Shoval, S, Benditt, E.P
Format: Article
Language:English
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Summary:Altered lipoprotein metabolism and vascular injury are considered to be major parts of the pathogenesis of atherosclerotic lesions. Serum amyloid A (SAA) is a family of acute-phase reactants found residing mainly on high density lipoproteins (HDL) in the circulation. Several functions for the SAAs have been proposed that could be important in atherosclerosis. These include involvement in cholesterol metabolism, participation in detoxification, depression of immune responses, and interference with platelet functions. Like other acute-phase reactants, the liver is a major site of SAA synthesis. However, studies in the mouse have revealed that several cell types including macrophages express SAA. Furthermore, we recently found that SAA mRNA expression can be induced in the human monocyte/macrophage cell line, THP-1. In the present study, human atherosclerotic lesions of coronary and carotid arteries were examined for expression of SAA mRNA by in situ hybridization. Surprisingly, SAA mRNA was found in most endothelial cells and some smooth muscle cells as well as macrophage-derived "foam cells," adventitial macrophages, and adipocytes. In addition, cultured smooth muscle cells expressed SAA1, SAA2, and SAA4 mRNAs when treated with interleukin 1 or 6 (IL-1 or IL-6) in the presence of dexamethasone. These findings give further credence to the notion that the SAAs are involved in lipid metabolism or transport at sites of injury and in atherosclerosis or may play a role in defending against viruses or other injurious agents such as oxidized lipids. Furthermore, expression of SAAs by endothelial cells is compatible with the evidence that SAA modulates platelet aggregation and function and possibly adhesion at the endothelial cell surface.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.8.3186