title: Citrulline increases cholesterol efflux from macrophages in vitro and ex vivo via ATP-binding cassette transporters.
abstract: Reverse cholesterol transport (RCT) is a mechanism critical to the anti-atherogenic property of HDL. Although citrulline contributes to the amelioration of atherosclerosis via endothelial nitric oxide production, it remains unclear whether it affects RCT. This study was undertaken to clarify the effects of citrulline on expressions of specific transporters such as ATP binding cassette transporters (ABC)A1 and ABCG1, and the cholesterol efflux from macrophages to apolipoprotein (apo) A-I or HDL in vitro and ex vivo. Citrulline increased ABCA1 and ABCG1 mRNA and protein levels in THP-1 macrophages, translating into enhanced apoA-I- and HDL-mediated cholesterol efflux. In the human crossover study, 8 healthy male volunteers (age 30-49 years) consumed either 3.2 g/day citrulline or placebo for 1 week. Citrulline consumption brought about significant increases in plasma levels of citrulline and arginine. Supporting the in vitro data, monocyte-derived macrophages (MDM) differentiated under autologous post-citrulline sera demonstrated enhancement of both apoA-I- and HDL-mediated cholesterol efflux through increased ABCA1 and ABCG1 expressions, compared to MDM differentiated under pre-citrulline sera. However, the placebo did not modulate these parameters. Therefore, in addition to improving endothelium function, citrulline might have an anti-atherogenic property by increasing RCT of HDL.
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Harumi
authors.initials: H
authors.lastname: Uto-Kondo
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ayaori
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakaya
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takiguchi
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Yakushiji
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Masatsune
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Division of Cardiology, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Terao
authors.affiliation: Division of Cardiology, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ozasa
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Grace Megumi
authors.initials: GM
authors.lastname: Sotherden
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Hosoai
authors.affiliation: Tokorozawa Heart Center, 2-6-61 Kamiarai, Tokorozawa, Saitama 359-1142, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Sakurada
authors.affiliation: Division of Anti-aging and Vascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikewaki
keywords: HDL; cholesterol; citrulline; macrophage; reverse cholesterol transport