Conjugated linoleic acid induces an atheroprotective macrophage Mφ2 phenotype and limits foam cell formation
Conjugated linoleic acid induces an atheroprotective macrophage Mφ2 phenotype and limits foam cell formation
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DOI：
10.1186/s12950-015-0060-9
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发表时间：
2015-02-19
影响因子：
5.1
通讯作者：
Belton, Orina
中科院分区：
文献类型：
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作者：
de Gaetano, Monica;Alghamdi, Kawthar;Belton, Orina
背景资料：动脉粥样硬化是心脏病发作和中风的根本原因，是一种进行性血脂异常和炎症性疾病，其中单核细胞衍生的巨噬细胞发挥关键作用。虽然大多数的机制，有助于动脉粥样硬化的进展已被确定，有有限的信息对那些管理回归。共轭亚油酸（CLA）是亚油酸的一组异构体，其双键的位置和/或几何形状不同。我们以前已经表明，一个特定的共轭亚油酸混合物（80：20顺式-9，反式-11：10，顺式-12-共轭亚油酸）诱导消退预先建立的动脉粥样硬化在体内，通过调节单核细胞/巨噬细胞功能。然而，CLA介导这种效应的确切机制仍有待阐明。方法：在这里，我们解决了CLA是否引发单核细胞向抗炎M phi 2巨噬细胞和检查单个CLA异构体和动脉粥样硬化保护混合物对单核细胞-巨噬细胞分化，细胞因子产生，泡沫细胞形成和胆固醇代谢的影响在人外周血单核细胞（HPBMC）衍生的巨噬细胞。结果：顺式-9，反式-11-CLA和抗动脉粥样硬化的80 ∶ 20 CLA混合物调节促炎介质的表达并调节巨噬细胞和泡沫细胞的炎性细胞因子谱。此外，顺式-9，反式-11-CLA和CLA共混物使HPBMC朝向抗炎M phi 2表型，其特征在于增加的清道夫受体（CD 36）和外排蛋白（ABCA-1）表达。此外，这种改变的巨噬细胞表型影响泡沫细胞形成，抑制ox-LDL积累并通过两种PPAR γ促进胆固醇流出。结论：这些数据增加了对CLA在动脉粥样硬化保护中调节的途径的理解，即抑制促炎性巨噬细胞表型的进行性获得。
Background: Atherosclerosis, the underlying cause of heart attack and strokes, is a progresive dyslipidemic and inflammatory disease where monocyte-derived macrophage cells play a pivotal role. Although most of the mechanisms that contribute to the progression of atherosclerosis have been identified, there is limited information on those governing regression. Conjugated linoleic acid (CLA) is a group of isomers of linoleic acid that differ in the position and/or geometry of their double bonds. We have previously shown that a specific CLA blend (80: 20 cis-9,trans-11:trans-10, cis-12-CLA) induces regression of pre-established atherosclerosis in vivo, via modulation of monocyte/macrophage function. However, the exact mechanisms through which CLA mediates this effect remain to be elucidated.Methods: Here, we address if CLA primes monocytes towards an anti-inflammatory M phi 2 macrophage and examine the effect of individual CLA isomers and the atheroprotective blend on monocyte-macrophage differentiation, cytokine generation, foam cell formation and cholesterol metabolism in human peripheral blood monocyte (HPBMC)-derived macrophages.Results: cis-9, trans-11-CLA and the atheroprotective 80: 20 CLA blend regulates expression of pro-inflammatory mediators and modulates the inflammatory cytokine profile of macrophages and foam cells. In addition, cis-9, trans-11-CLA and CLA blend primes HPBMCs towards an anti-inflammatory M phi 2 phenotype, characterised by increased scavenger receptor (CD36) and efflux protein (ABCA-1) expression. Furthermore, this altered macrophage phenotype impacts on foam cell formation, inhibiting ox-LDL accumulation and promoting cholesterol efflux via both PPAR gamma. and LXR alpha dependent pathways.Conclusion: The data increases the understanding of the pathways regulated by CLA in atheroprotection, namely, inhibiting the progressive acquisition of a pro-inflammatory macrophage phenotype.