Regulation of ACAT in multiple risk factor syndrome

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Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) was regarded as a major ACAT isoform expressed in human macrophages. However, the current immunohistochemical studies with an ACAT2 antibody demonstrated significant expression of ACAT2 in macrophage-foam cells in human atherosclerotic lesions. All the macrophages in the lesions expressed ACAT1 while 70-80% of the macrophages expressed ACAT2. Immunoblot and RT-PCR analyses of cultured human monocyte-macrophages demonstrated that immature macrophages expressed only ACAT1 while fully differentiated macrophages expressed both ACAT1 and ACAT2. Additional immunoblot and RT-PCR analyses showed that mouse peritoneal exudate macrophages expressed both ACAT1 and ACAT2 while mouse resident peritoneal macrophages expressed only ACAT1. We conclude that under various pathological conditions, fully differentiated macrophages express ACAT2 in addition to ACAT1.