Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages.
Plasma high density lipoprotein (HDL)-cholesterol levels are inversely correlated to the risk of atherosclerotic cardiovascular diseases. Reverse cholesterol transport (RCT) is one of the major protective systems against atherosclerosis, in which HDL particles play a crucial role to carry cholesterol derived from peripheral tissues to the liver. Recently, ATP-binding cassette transporters (ABCA1, ABCG1) and scavenger receptor (SR-BI) have been identified as important membrane receptors to generate HDL by removing cholesterol from foam cells. Adiponectin (APN) secreted from adipocytes is one of the important molecules to inhibit the development of atherosclerosis. Epidemiological studies have revealed a positive correlation between plasma HDL-cholesterol and APN concentrations in humans, although its mechanism has not been clarified. Therefore, in the present study, we investigated the role of APN on RCT, in particular, cellular cholesterol efflux from human monocyte-derived and APN-knockout (APN-KO) mice macrophages. APN up-regulated the expression of ABCA1 in human macrophages, respectively. ApoA-1-mediated cholesterol efflux from macrophages was also increased by APN treatment. Furthermore, the mRNA expression of LXRalpha and PPARgamma was increased by APN. In APN-KO mice, the expression of ABCA1, LXRalpha, PPARgamma, and apoA-I-mediated cholesterol efflux was decreased compared with wild-type mice. In summary, APN might protect against atherosclerosis by increasing apoA-I-mediated cholesterol efflux from macrophages through ABCA1-dependent pathway by the activation of LXRalpha and PPARgamma.
Tsubakio-Yamamoto
Kazumi
K
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamamdaoka, Suita, Osaka 565-0871, Japan.
Matsuura
Fumihiko
F
Koseki
Masahiro
M
Oku
Hiroyuki
H
Sandoval
Jose C
JC
Inagaki
Miwako
M
Nakatani
Kazuhiro
K
Nakaoka
Hajime
H
Kawase
Ryota
R
Yuasa-Kawase
Miyako
M
Masuda
Daisaku
D
Ohama
Tohru
T
Maeda
Norikazu
N
Nakagawa-Toyama
Yumiko
Y
Ishigami
Masato
M
Nishida
Makoto
M
Kihara
Shinji
S
Shimomura
Iichiro
I
Yamashita
Shizuya
S
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D052242:Adiponectin / Q000235:genetics / Q000502:physiology*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology*; D001692:Biological Transport; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D006801:Humans; D000071518:Liver X Receptors; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis
C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D052242:Adiponectin; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B