EXPRESSION OF APOLIPOPROTEIN SERUM AMYLOID-A MESSENGER-RNA IN HUMAN ATHEROSCLEROTIC LESIONS AND CULTURED VASCULAR CELLS - IMPLICATIONS FOR SERUM AMYLOID-A FUNCTION

Altered lipoprotein metabolism and vascular injury are considered to b e major parts of the pathogenesis of atherosclerotic lesions. Serum am yloid A (SAA) is a family of acute-phase reactants found residing main ly on high density lipoproteins (HDL) in the circulation. Several func tions for the SAAs have been proposed that could be important in ather osclerosis. These include involvement in cholesterol metabolism, parti cipation in detoxification, depression of immune responses, and interf erence 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 SA A. Furthermore, we recently found that SAA mRNA expression can be indu ced 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. Sur prisingly, SAA mRNA was found in most endothelial cells and some smoot h muscle cells as well as macrophage-derived ''foam cells,'' adventiti al macrophages, and adipocytes. In addition, cultured smooth muscle ce lls expressed SAA1, SAA2, and SAA4 mRNAs when treated with interleukin 1 or 6 (IL-1 or IL-6) in the presence of dexamethasone. These finding s give further credence to the notion that the SAAs are involved in li pid metabolism or transport at sites of injury and in atherosclerosis or may play a role in defending against viruses or other injurious age nts such as oxidized lipids. Furthermore, expression of SAAs by endoth elial cells is compatible with the evidence that SAA modulates platele t aggregation and function and possibly adhesion at the endothelial ce ll surface.