The anti-atherogenic potential of serum amyloid A peptides.

Serum amyloid A (SAA) inhibits acyl coenzyme A cholesterol acyltransferase and enhances cholesterol esterase activities, shifting stored esterified cholesterol to free cholesterol (the exportable form). The SAA domains responsible for these enzyme-modifying properties have been identified. These peptides are sufficiently small to be synthetically prepared to GMP quality and used in vivo to alter the progression of aortic lipid lesions in models of atherogenesis, suggesting that they may be clinically useful. The residues critical for peptide function are the foundation for corresponding small-molecule development. In association with SAA studies, a novel macrophage in vivo assay is described that monitors macrophage cholesterol efflux, as well as its utility in the study of anti-atherogenic compounds, and its adaptation for clinical use. A brief history of the role of SAA in amyloid A amyloidosis and its potential role in atherogenesis is included, along with a description of the function of SAA in mobilizing macrophage cholesterol for export.