Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL) in RAW264.7 cells. Treatment with sesamin (10 mu M) significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL). Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPAR gamma, LXR alpha, and ABCG1, and increased the transcriptional activity of PPAR gamma The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPAR gamma. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPAR gamma-LXR alpha-ABCG1 pathway.
基金:
Natural Sciences Foundation of ChinaNational Natural Science Foundation of China [81000135, 81001437]
第一作者机构:[1]Capital Med Univ, Beijing Anzhen Hosp, Cardiac Surg Intens Care Unit, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing 100029, Peoples R China;
通讯作者:
通讯机构:[2]Chinese Acad Med Sci, Inst Med Plant Dev, Pharmacol & Toxicol Res Ctr, Beijing 100094, Peoples R China;[3]Peking Union Med Coll, Beijing 100094, Peoples R China;
推荐引用方式(GB/T 7714):
Liu Nan,Wu Chongming,Sun Lizhong,et al.Sesamin Enhances Cholesterol Efflux in RAW264.7 Macrophages[J].MOLECULES.2014,19(6):7516-7527.doi:10.3390/molecules19067516.