De Caterina R, Libby P
Vascular Medicine and Atherosclerosis Unit, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Lipids. 1996 Mar;31 Suppl:S57-63. doi: 10.1007/BF02637052.
Dietary balance of long-chain fatty acids (FA) may influence human susceptibility to pathological processes which involve the interaction of leukocytes with vascular endothelium, such as atherogenesis and inflammation. Such interaction is largely mediated by the de novo or increased expression of endothelial leukocyte adhesion molecules on vascular endothelial cells, able to tether and stably bind leukocytes onto the vessel wall, and by the production of leukocyte chemoattractants. Endothelial cells do not normally support high levels of leukocyte adhesion. They do so, however, when exposed to a number of stimuli, such as oxidized low density lipoprotein bacterial lipopolysaccharides, and inflammatory cytokines, which induce phenotypic changes generally referred to as "endothelial activation." We compared various FA in their ability to modulate endothelial activation by cytokines. FA included linoleic, arachidonic, oleic, eicosapentaenoic and, docosa-hexaenoic acid (DHA) as representatives of the n-6, n-3 polyunsaturated FA and of the monounsaturated FA. The n-3 FA DHA, and, to a lesser extent, oleate, at nutritionally compatible concentrations, were able to reduce endothelial expression of Vascular Cell and Adhesion Molecule-1 (VCAM-1). In further studies, DHA dose- and time-dependently reduced also the expression of E-selectin, Intercellular Adhesion Molecule-1, interleukin (IL)-6 and IL-8, in response to IL-1, IL-4, tumor-necrosis factor, or bacterial endotoxin. The magnitude of this effect paralleled its incorporation into cellular phospholipids. Also, coordinate with reduced surface adhesion molecule expression, DHA reduced the adhesion of human monocytes and of monocytic U937 cells to cytokine-stimulated endothelial cells. These effects were accompanied by a quantitatively consistent reduction in VCAM-1 mRNA, indicating a pretranslational control of adhesion molecule gene expression. These novel properties of FA as modulators of endothelial activation may help to explain the influence of dietary FA intake on atherogenesis and inflammation.
长链脂肪酸（FA）的饮食平衡可能会影响人体对涉及白细胞与血管内皮相互作用的病理过程的易感性，如动脉粥样硬化和炎症。这种相互作用很大程度上是由血管内皮细胞上从头合成或增加表达的内皮白细胞粘附分子介导的，这些分子能够将白细胞束缚并稳定地结合在血管壁上，还由白细胞趋化因子的产生介导。内皮细胞通常不支持高水平的白细胞粘附。然而，当暴露于多种刺激时，如氧化型低密度脂蛋白、细菌脂多糖和炎性细胞因子，它们就会这样做，这些刺激会诱导通常被称为“内皮激活”的表型变化。我们比较了各种脂肪酸调节细胞因子诱导的内皮激活的能力。脂肪酸包括亚油酸、花生四烯酸、油酸、二十碳五烯酸和二十二碳六烯酸（DHA），分别作为n-6、n-3多不饱和脂肪酸和单不饱和脂肪酸的代表。在营养相容浓度下，n-3脂肪酸DHA以及程度较轻的油酸能够降低血管细胞粘附分子-1（VCAM-1）的内皮表达。在进一步的研究中，DHA还剂量和时间依赖性地降低了E-选择素、细胞间粘附分子-1、白细胞介素（IL）-6和IL-8的表达，这些表达是对IL-1、IL-4、肿瘤坏死因子或细菌内毒素的反应。这种效应的程度与其掺入细胞磷脂的程度平行。此外，与表面粘附分子表达的降低相一致，DHA降低了人单核细胞和单核细胞U937细胞对细胞因子刺激的内皮细胞的粘附。这些效应伴随着VCAM-1 mRNA的定量一致减少，表明粘附分子基因表达的转录前控制。脂肪酸作为内皮激活调节剂的这些新特性可能有助于解释饮食中脂肪酸摄入对动脉粥样硬化和炎症的影响。
