title: Induction of ABCA1 by overexpression of hormone-sensitive lipase in macrophages.
abstract: Initial step toward the reverse-cholesterol transport is cholesterol efflux that is mediated by the ATP-binding cassette transporter A1 (ABCA1). However, it is unknown how the cholesteryl ester (CE) hydrolysis induces the expression of the ABCA1 gene. Overexpression of hormone-sensitive lipase (HSL) increased the hydrolysis of CE and stimulated the expression of ABCA1 gene at the transcriptional level in RAW 264.7 macrophages. The stimulatory effects of the HSL overexpression and cholesterol loading on the ABCA1 promoter activity were additive. Mutational analyses of the promoter of ABCA1 identified the responsible element as the direct repeat-4 (DR-4) that binds LXR/RXR heterodimers. In conclusion, stimulation of hydrolysis of CE in macrophages induces the expression of ABCA1 gene primarily via the LXR-dependent pathway and can be useful for the prevention of atherosclerosis.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Tazoe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yagyu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Eto
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Nagashima
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Inaba
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi