Human ACAT1 gene expression and its involvement in the development of atherosclerosis.

Atherosclerosis is caused by a series of pathologic changes at the cellular level, with formation of macrophage-derived foam cells occurring at an early stage. Most of the cholesteryl esters in macrophage foam cells are produced by the enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT). Two ACAT genes, Acat1 and Acat2, exist in mammals. In the monocyte-macrophages, ACAT1 is the major isoenzyme and is a drug target for atherosclerosis treatment. Various proatherogenic stimuli, including interferon-gamma and dexamethasone, cause upregulation of human Acat1 expression in macrophages. Thus, it should be possible to find antagonist(s) to downregulate human Acat1 expression. A greater understanding of human Acat1 expression may provide scientists with opportunities for novel therapeutic approaches to combat atherosclerosis.