論文 - 詳細
| RRC ID | 18677 |
|---|---|
| 著者 | Nakaya K, Ayaori M, Uto-Kondo H, Hisada T, Ogura M, Yakushiji E, Takiguchi S, Terao Y, Ozasa H, Sasaki M, Komatsu T, Ohsuzu F, Ikewaki K. |
| タイトル | Cilostazol enhances macrophage reverse cholesterol transport in vitro and in vivo. |
| ジャーナル | Atherosclerosis |
| Abstract |
OBJECTIVE:Recent failure of an HDL-cholesterol raising strategy using a cholesteryl ester transfer protein inhibitor highlights the importance of the anti-atherogenic function rather than plasma concentration of HDL. Cilostazol, a selective inhibitor of phosphodiesterase 3, has been widely used in patients with atherosclerotic diseases and is known to increase HDL-cholesterol. However, it remains unclear whether cilostazol enhances anti-atherogenic properties by promoting reverse cholesterol transport (RCT), a major anti-atherogenic function of HDL. METHODS AND RESULTS:We observed that treatment of THP-1 macrophages, human monocyte-derived macrophages, and RAW264.7 cells with cilostazol increased ABCA1 and ABCG1 expression in a concentration-dependent manner, translating into enhanced apoA-I- and HDL-mediated cholesterol efflux from the macrophages. However, other cyclic AMP (cAMP)-elevating agents did not increase ABCA1 gene expression in THP-1 macrophages. Cilostazol did not change intracellular cAMP levels in THP-1 macrophages and RAW264.7 cells, and a protein kinase A (PKA) inhibitor did not affect cilostazol-induced ABCA1 and ABCG1 expression. To further investigate RCT in vivo, (3)H-cholesterol-labeled and acetyl LDL-loaded RAW264.7 cells were intraperitoneally injected into mice and the appearance of the (3)H-tracer was monitored in plasma, liver, and feces. Supporting the in vitro data, cilostazol was found to significantly increase (3)H-tracer levels in both plasma and feces. CONCLUSIONS:These findings indicate that cilostazol might provide anti-atherosclerotic effects by promoting RCT through increased ABCA1/G1 expression in macrophages. |
| 巻・号 | 213(1) |
| ページ | 135-41 |
| 公開日 | 2010-11-1 |
| DOI | 10.1016/j.atherosclerosis.2010.07.024 |
| PII | S0021-9150(10)00569-1 |
| PMID | 20723893 |
| MeSH | Bile / metabolism Biological Transport Cholesterol / metabolism* Cholesterol, HDL / metabolism Cilostazol Cyclic AMP / metabolism Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism Humans In Vitro Techniques Liver / metabolism Macrophages / metabolism* Models, Biological Phosphodiesterase 3 Inhibitors / pharmacology Reverse Transcriptase Polymerase Chain Reaction Tetrazoles / pharmacology* |
| IF | 3.919 |
| 引用数 | 28 |
| WOS 分野 | CARDIAC & CARDIOVASCULAR SYSTEMS PERIPHERAL VASCULAR DISEASE |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) THP-1(RCB1189) |