| Summary: | Homozygotes for loss-of-function mutations in ABCA1 cause Tangier disease. The phenotype of their markedly reduced or loss of blood high-density lipoprotein (HDL) cholesterol, as well as examination of ATP-binding cassette transporter A1 (ABCA1)-deficient mice, proved that ABCA1 is a key player in HDL production. The ABCA1-mediated cholesterol efflux is the first step in the reverse cholesterol transport system and understanding the regulation of its expression was expected to lead to the development of anti-atherosclerotic drugs. However, from the viewpoint of intracellular cholesterol homeostasis, it is difficult to say that simple activation of ABCA1 or promotion of cholesterol efflux is a good strategy. To date, there is no evidence that HDL-increasing drugs by enhancing ABCA1 expression prevent atherosclerotic disease in humans. On the other hand, in situations where intracellular cholesterol homeostasis is disrupted by inflammation, aging, or metabolic abnormalities, a strategy that restores reduced ABCA1 expression and cholesterol efflux in a timely and localized manner may be useful.
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