IN VIVO INFLUENCE OF SERUM AMYLOID A 2.1 AND ITS ACTIVE DOMAINS ON MACROPHAGE CHOLESTEROL EXPORT

摘要

The accumulation of lipids, especially cholesterol, in several vascular cell types such as macrophages and smooth muscle cells, is a defining pathologic feature of atherosclerosis. This accumulation is likely due to an imbalance between the biosynthesis, uptake and esterification of cholesterol on the one hand, and, on the other hand, the de-esterification and export of unesterified macrophage cholesterol. Serum amyloid A (SAA) isoforms 1.1 and 2.1 are acute phase proteins produced by the liver in response to any acute tissue injury. Previously we have shown that SAA 2.1, but not 1.1, suppresses acyl-CoA:cholesterol acyl transferase (ACAT) and enhances cholesteryl ester hydrolase (CEH) activities in cholesterol-laden murine macrophages and in so doing shifts cholesterol into its transportable state increasing its rate of export (1). The present study further characterizes and defines the effect of SAA2.1 on cholesterol efflux from cholesterol-laden macrophages in vivo.