Fatty acid modulation of endothelial activation
Fatty acid modulation of endothelial activation
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DOI：
10.1093/ajcn/71.1.213s
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发表时间：
2000-01-01
影响因子：
7.1
通讯作者：
Libby, P
中科院分区：
文献类型：
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作者：
De Caterina, R;Liao, JK;Libby, P
长链脂肪酸的膳食平衡可能影响涉及白细胞-内皮相互作用的过程，例如动脉粥样硬化形成和炎症，其涉及白细胞粘附分子的内皮表达增加或内皮活化。我们比较了各种饱和、单不饱和和多不饱和脂肪酸调节内皮激活的能力。消耗n-3脂肪酸二十二碳六烯酸（DHA; 22：6 n-3）可降低血管细胞粘附分子I（VCAM-1）、E-选择素、细胞间粘附分子1（ICAM-1）、白细胞介素6（IL-6）和IL-8对IL-1、IL-4、肿瘤坏死因子或细菌内毒素的反应的内皮表达，半数最大抑制浓度（IC 50）为1-25 μ mol，即在营养可达到的血浆浓度范围内。这种作用的大小决定了它与细胞磷脂的结合。DHA还降低了人单核细胞和单核细胞U937细胞对姜黄素刺激的内皮细胞的粘附。这些效应伴随着VCAM-1信使RNA的减少，表明存在翻译前效应。为了评估VCAM-1抑制活性的结构脂肪酸决定因素，我们比较了各种饱和、单不饱和和n-6和n-3多不饱和脂肪酸的VCAM-1抑制活性。饱和脂肪酸不抑制精氨酸诱导的粘附分子表达。然而，观察到的抑制活性的逐步增加与饮食摄入的脂肪酸具有相同的链长，但增加双键，即，从单不饱和的n-6，进一步，n-3脂肪酸。因此，与n-6脂肪酸相比，n-3脂肪酸在抑制内皮活化方面具有更大的活性，双键的数量越多似乎越关键。这些性质可能与n-3脂肪酸的抗动脉粥样硬化和抗动脉粥样硬化性质有关。
Dietary balance of long-chain fatty acids may influence processes involving leukocyte-endothelial interactions, such as atherogenesis and inflammation, that involve increased endothelial expression of leukocyte adhesion molecules, or endothelial activation. We compared the ability of various saturated, monounsaturated, and polyunsaturated fatty acids to modulate endothelial activation. Consumption of the n-3 fatty acid docosahexaenoic acid (DHA; 22:6n-3) reduced endothelial expression of vascular cell adhesion molecule I (VCAM-1), E-selectin, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), and IL-8 in response to IL-1, IL-4, tumor necrosis factor, or bacterial endotoxin, with a half-maximal inhibitory concentration (IC50) of 1-25 mu mol, ie, in the range of nutritionally achievable plasma concentrations. The magnitude of this effect paralleled its incorporation into cellular phospholipids. DHA also reduced the adhesion of human monocytes and monocytic U937 cells to cytokine-stimulated endothelial cells. These effects were accompanied by a reduction in VCAM-1 messenger RNA, indicating a pretranslational effect. To assess structural fatty acid determinants of VCAM-1 inhibitory activity, we compared various saturated, monounsaturated, and n-6 and n-3 polyunsaturated fatty acids for their VCAM-1 inhibitory activity. Saturated fatty acids did not inhibit cytokine-induced expression of adhesion molecules. However, a progressive increase in inhibitory activity was observed with dietary intake of fatty acids with the same chain length but increasing double bonds, ie, from monounsaturated to n-6 and, further, to n-3 fatty acids. Thus, the greater number of double bonds seems critical for the greater activity of n-3 compared with n-6 fatty acids in inhibiting endothelial activation. These properties are likely to be relevant to the antiatherogenic and antiinflammatory properties of n-3 fatty acids.