Long-chain saturated fatty acids induce pro-inflammatory responses and impact endothelial cell growth

Long-chain saturated fatty acids induce pro-inflammatory responses and impact endothelial cell growth
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DOI:
10.1016/j.clnu.2009.10.008
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发表时间:
2010-08-01
期刊:
影响因子:
6.3
通讯作者:
Siddiqui, Rafat A.
Siddiqui, Rafat A.
中科院分区:
医学1区
文献类型:
--
作者:
Harvey, Kevin A.;Walker, Candace L.;Siddiqui, Rafat A.

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背景和目标:饱和脂肪酸(SFA)是肠内和胃肠外制剂的重要成分,与心血管并发症有关。然而,SFA对血管炎症的影响尚不清楚。内皮细胞在急性炎症反应中起重要作用。因此,我们评估了不同链长的SFAs对EC functions.Methods的急性影响:内皮细胞与各种SFAs培养。通过WST-1试验测定生长和细胞毒性。流式细胞术检测细胞凋亡和促炎性粘附分子(ICAM-1)表达。结果:长链SFA(C14:0-C20:0)对EC生长具有抑制作用,且呈链长依赖性。中链脂肪酸(C6:0-C12:0)对EC生长没有显著影响。相比之下,短链SFA(C4:0)刺激细胞生长。硬脂酸诱导的EC凋亡和坏死明显多于棕榈酸和肉豆蔻酸。硬脂酸(>10 μ M)处理也显著增加ICAM-1表达。硬脂酸的促炎反应通过I kappa B-α和NF-κ B B的磷酸化以剂量依赖的方式证实。结论:长链SFA可以诱导促炎反应并显著影响EC的生长和活力。我们的数据表明,胃肠外制剂中长链SFA的存在可能对血管系统产生有害影响。(C)2009 Elsevier Ltd和欧洲临床营养与代谢学会。All rights reserved.
Background & aims: Saturated fatty acids (SFAs), significant components of enteral and parenteral formulations, have been linked to cardiovascular complications. However, the effect of SFAs upon vascular inflammation is less clear. Endothelial cells (EC) play an important role in the acute inflammatory responses. We, therefore, evaluated the acute effects of different chain-length SFAs upon EC functions.Methods: Endothelial cells were cultured with various SFAs. Growth and cytotoxicity were determined by WST-1 assay. Apoptosis and pro-inflammatory adhesion molecule (ICAM-1) expression was assayed using flow cytometry. Activation of NF-kappa B was analyzed using western blot analysis.Results: Long-chain SFAs (C14:0-C20:0) inhibited EC growth in a chain-length dependent manner. Medium-chain SFAs (C6:0-C12:0) did not significantly affect EC growth. In contrast, the short-chain SFA (C4:0) stimulated cellular growth. Stearic acid induced significantly more EC apoptosis and necrosis than palmitic acid or myristic acids. Stearic acid (>10 mu M) treatment also significantly increased ICAM-1 expression. Stearic acid's pro-inflammatory response was confirmed by phosphorylation of I kappa B-alpha and NF-kappa B in a dose dependent manner.Conclusions: Long-chain SFAs can induce pro-inflammatory responses and significantly impact growth and viability of EC. Our data suggest that the presence of long-chain SFAs in parenteral formulations may have harmful effects on the vascular system. (C) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.