Zhang Chi, Yin Weidong, Liao Duanfang, Huang Liang, Tang Chaoke, Tsutsumi Kazuhiko, Wang Zongbao, Liu Yi, Li Qinkai, Hou Hongjie, Cai Manbo, Xiao Junxia
Institute of Cardiovascular Research, Nanhua University Medical School, Hengyang, Hunan 421001, China.
J Lipid Res. 2006 Sep;47(9):2055-63. doi: 10.1194/jlr.M600226-JLR200. Epub 2006 Jun 28.
It is widely believed that high density lipoprotein-cholesterol (HDL-C) functions to transport cholesterol from peripheral cells to the liver by reverse cholesterol transport (RCT), a pathway that may protect against atherosclerosis by clearing excess cholesterol from arterial cells. A cellular ATP binding cassette transporter called ABCA1 mediates the first step of RCT. NO-1886 has been proven to be highly effective at increasing HDL-C and reducing atherosclerosis. However, the mechanism of atherosclerosis inhibition for NO-1886 is not fully understood. In this study, the effects of NO-1886 on ABCA1 were investigated in high-fat/high-sucrose/high-cholesterol-fed Chinese Bama minipigs. Administration of NO-1886 (0.1 g/kg body weight/day) in the diet for 5 months significantly reduced atherosclerosis lesions and significantly increased plasma HDL-C and apolipoprotein A-I levels. The mRNA and protein levels of ABCA1 in the liver, retroperitoneal adipose tissue, and aorta were increased by NO-1886 as well. Multivariate linear regression analysis showed that the levels of LPL in plasma and the levels of ABCA1 in aorta were independently associated with the atherosclerotic lesion area. In addition, NO-1886 upregulated liver X receptor alpha and affected the expression of scavenger receptor class B type I in the liver. These results demonstrate that the mechanism of atherosclerosis inhibition for NO-1886 is associated with its effect on ABCA1.
人们普遍认为，高密度脂蛋白胆固醇（HDL-C）通过逆向胆固醇转运（RCT）将胆固醇从外周细胞转运至肝脏，该途径可通过清除动脉细胞中的过量胆固醇来预防动脉粥样硬化。一种名为ABCA1的细胞ATP结合盒转运蛋白介导了RCT的第一步。已证实NO-1886在升高HDL-C和减轻动脉粥样硬化方面非常有效。然而，NO-1886抑制动脉粥样硬化的机制尚未完全明确。在本研究中，在高脂/高糖/高胆固醇喂养的中国巴马小型猪中研究了NO-1886对ABCA1的影响。在饮食中给予NO-1886（0.1 g/kg体重/天）5个月可显著减少动脉粥样硬化病变，并显著提高血浆HDL-C和载脂蛋白A-I水平。NO-1886还可提高肝脏、腹膜后脂肪组织和主动脉中ABCA1的mRNA和蛋白水平。多变量线性回归分析表明，血浆中LPL水平和主动脉中ABCA1水平与动脉粥样硬化病变面积独立相关。此外，NO-1886上调肝脏X受体α并影响肝脏中B类I型清道夫受体的表达。这些结果表明，NO-1886抑制动脉粥样硬化的机制与其对ABCA1的作用有关。
