| RRC ID |
19343
|
| 著者 |
Matsuki K, Tamasawa N, Yamashita M, Tanabe J, Murakami H, Matsui J, Imaizumi T, Satoh K, Suda T.
|
| タイトル |
Metformin restores impaired HDL-mediated cholesterol efflux due to glycation.
|
| ジャーナル |
Atherosclerosis
|
| Abstract |
High-density lipoprotein (HDL) mediates cholesterol efflux, which is the initial and rate-limiting step of reverse cholesterol transport. The present study was undertaken to evaluate the effect, on macrophage cholesterol efflux, of functional modification of HDL by its glycation. We also investigated the effects of the glycation-inhibitors metformin (MF) and aminoguanidine (AG) on glycated HDL-mediated cholesterol efflux. Human plasma HDL (5mg protein/mL) was glycated by incubation with 3-deoxyglucosone (3-DG). Glycation was monitored by measuring carboxymethyl-lysine (CML). HDL-mediated cholesterol efflux was determined using human THP-1-derived macrophages pre-labeled with [(3)H]-cholesterol. To measure expression of potential factors related to the efflux in the macrophages, ATP-binding cassette transporter (ABC) G1 was analyzed by real-time quantitative RT-PCR and Western blot. Glycation of HDL significantly reduced the HDL-mediated cholesterol efflux from THP-1-derived macrophages (87.7+/-4.2% of control, n=9, p<0.0001). In the presence of metformin or aminoguanidine (100mM), glycated HDL-mediated cholesterol efflux was restored to 97.5+/-4.3% and 96.9+/-3.1%, respectively. Exogenous HDL reduced ABCG1 mRNA and protein expression in THP-1-derived macrophages, but glycation deprived HDL of this effect. We conclude that glycated HDL particles are ineffective as acceptors of ABCG1-mediated cholesterol efflux; and this may explain, at least in part, accelerated atherosclerosis in diabetic patients. Metformin serves as a possible candidate to restore impaired cholesterol efflux and reverse cholesterol transport.
|
| 巻・号 |
206(2)
|
| ページ |
434-8
|
| 公開日 |
2009-10-1
|
| DOI |
10.1016/j.atherosclerosis.2009.03.003
|
| PII |
S0021-9150(09)00209-3
|
| PMID |
19376519
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily G, Member 1
ATP-Binding Cassette Transporters / metabolism
Cells, Cultured
Cholesterol / metabolism*
Deoxyglucose / analogs & derivatives
Deoxyglucose / metabolism
Gene Expression / drug effects
Glycation End Products, Advanced / antagonists & inhibitors
Glycosylation
Guanidines / pharmacology
Humans
Lipoproteins, HDL / chemistry
Lipoproteins, HDL / physiology*
Macrophages / metabolism*
Metformin / pharmacology*
|
| IF |
3.919
|
| 引用数 |
31
|
|
WOS 分野
|
CARDIAC & CARDIOVASCULAR SYSTEMS
PERIPHERAL VASCULAR DISEASE
|
| リソース情報 |
| ヒト・動物細胞 |
THP-1(RCB1189) |
