Stachowska Ewa, Baskiewicz Magdalena, Marchlewicz Mariola, Czupryńska Katarzyna, Kaczmarczyk Mariusz, Wiszniewska Barbara, Machaliński Bogusław, Chlubek Dariusz
Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Szczecin, Poland.
Acta Biochim Pol. 2010;57(3):379-84.
Atherosclerosis is an inflammatory disease characterised by the accumulation of lipids and their metabolites in the artery wall. During inflammation circulating LDL are taken up by macrophages through two major scavenger receptors: CD36 and scavenger receptor A (SRA). Fatty acids that are common in food, e.g. linoleic acid and n-3 unsaturated fatty acids can modulate expression of CD36 on the macrophage surface. Conjugated linoleic acid isomers (CLA) that originate from the human diet, have demonstrated antiatherogenic properties in several experiments. Animal study evidenced that CLA could induce resolution of plaque by activation of peroxisome proliferator activated receptors and down-regulation of pro-inflammatory genes. Less unequivocal results were obtained in human studies (on the CLA effects on the inflammatory process). Therefore in this study we investigated the influence of CLA on CD36 expression and lipid accumulation in human macrophages. Macrophages were incubated with 30 μM cis-9,trans-11 CLA, trans-10,cis-12 CLA or linoleic acid for 48 h. After that, expression of CD36 as well as accumulation of lipids were measured by flow cytometry, microscopy and a spectroscopic method. We demonstrate that both cis-9,trans-11 C 18 : 2 CLA and linoleic acid slightly elevated expression of CD36, whereas second isomer — trans-10,cis-12 CLA — did not. Nevertheless, only trans-10,cis-12 CLA triggered delipidation of macrophages, that is decreased triacylglycerols concentration. Also in human adipocytes, trans-10,cis-12 CLA causes cell delipidation by reduction of PPAR receptor expression. We propose a similar mechanism for human macrophages/foam cells.
动脉粥样硬化是一种炎症性疾病，其特征是脂质及其代谢产物在动脉壁中积累。在炎症过程中，循环中的低密度脂蛋白（LDL）通过两种主要的清道夫受体被巨噬细胞摄取：CD36和清道夫受体A（SRA）。食物中常见的脂肪酸，如亚油酸和n-3不饱和脂肪酸，可以调节巨噬细胞表面CD36的表达。源自人类饮食的共轭亚油酸异构体（CLA）在多项实验中已证明具有抗动脉粥样硬化特性。动物研究表明，CLA可通过激活过氧化物酶体增殖物激活受体和下调促炎基因来诱导斑块消退。在人体研究中（关于CLA对炎症过程的影响）获得的结果不太明确。因此，在本研究中，我们研究了CLA对人巨噬细胞中CD36表达和脂质积累的影响。将巨噬细胞与30μM顺式-9，反式-11 CLA、反式-10，顺式-12 CLA或亚油酸孵育48小时。之后，通过流式细胞术、显微镜检查和光谱法测量CD36的表达以及脂质的积累。我们证明，顺式-9，反式-11 C 18 : 2 CLA和亚油酸均略微提高了CD36的表达，而第二种异构体——反式-10，顺式-12 CLA——则没有。然而，只有反式-10，顺式-12 CLA引发了巨噬细胞的脂质清除，即三酰甘油浓度降低。同样在人脂肪细胞中，反式-10，顺式-12 CLA通过降低PPAR受体表达导致细胞脂质清除。我们提出人巨噬细胞/泡沫细胞存在类似机制。
