Endogenous ApoA-I expression in macrophages: A potential target for protection against atherosclerosis

ApoA-I is a major protein component of high-density lipoprotein (HDL) that is widely known for regulating cholesterol trafficking and inflammatory and immune responses and for protecting against atherosclerosis. ApoA-I is generally considered to be synthesized in the liver (hepatocytes) and small intestine (enterocytes). However, computer analysis of ApoA-I has shown that the ApoA-I gene may be expressed in not only hepatocytes and enterocytes but also monocyte-macrophage cells, dendritic cells (DCs) and T cells. ApoA-I expression has been detected in THP-1 monocytes and macrophages, peripheral blood mononuclear cells (PBMCs) from postmenopausal women, human PBMC-derived monocytes and macrophages, mouse peritoneal macrophages, etc. Endogenous ApoA-I in macrophages has anti-inflammatory and cholesterol efflux effects. However, our understanding of the detailed roles of macrophage-synthesized ApoA-I is still at an early stage and very limited. More experiments are needed to elucidate the exact roles of endogenous ApoA-I in macrophages. Several lines of evidence indicate that recombinant exogenous human ApoA-I in mouse macrophages increases cholesterol efflux and thus reduces atherosclerosis development. Considering the antiatherogenic effect of exogenous ApoA-I overexpression in mouse macrophages, better understanding the role and mechanisms underlying macrophage-synthesized ApoA-I in atherosclerosis will enable macrophage-synthesized ApoA-I therapy to open new avenues for reducing the risk of atherosclerosis.