Apolipoprotein serum amyloid A down-regulates smooth-muscle cell lipid biosynthesis

The addition of acute-phase apolipoprotein serum amyloid A (SAA) to culture d aortic smooth-muscle cells caused a decrease in the incorporation of [C-1 4]acetate into lipids. Optimal inhibition of lipid biosynthesis was achieve d with 2 mu M SAA, and the effect was maintained for up to 1 week when SAA was included in the culture medium. Lipid extracts were subjected to TLC an d it was determined that the SAA-induced decrease in [C-14]acetate incorpor ation into lipids was attributable to decreases in cholesterol, phospholipi d and triglyceride levels. The accumulated mass of cholesterol and phosphol ipid in SAA-treated cultures was significantly less than that of controls, with no change in the accumulated protein. Moreover, SAA had no effect on e ither protein synthesis or DNA synthesis, suggesting that SAA specifically alters lipid synthesis. By using a peptide corresponding to the cholesterol -binding domain of acute-phase SAA (amino acids 1-18), it was shown that th is region of the molecule was as effective as the full-length protein in de creasing lipid synthesis and the accumulation of cholesterol and phospholip id. The implications of these findings for atherosclerosis and Alzheimer's disease are discussed.