Faculty of Fundamental and Applied Sciences, University of Poitiers, 86000 Poitiers, France.
Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
Cells. 2022 Jul 14;11(14):2202. doi: 10.3390/cells11142202.
Lipid emulsions are crucial for life-saving total parenteral nutrition (TPN). Their composition provides a high amount of essential fatty acids and calories for millions of patients with serious diseases. Nevertheless, several TPN-mediated side-effects have been reported in over 90% of patients. This project aimed to investigate the effect of a high amount of ω3 fatty acids (Omegaven) emulsion vs. a high amount of ω6 fatty acids (Intralipid) emulsions on the endothelial barrier function. EA.hy926 cell line was cultured and incubated with 0.01, 0.1, and 1 mM lipid emulsions. The influence of these lipid emulsions on the barrier function was assessed using ECIS technology, immunofluorescent microscopy, viability measurements by flow cytometry, multiplex cytokines analysis, and qRT-PCR. BODIPY staining confirmed the uptake of fatty acids by endothelial cells. ECIS measurements demonstrated that a high concentration of Omegaven prevents barrier formation and impairs the barrier function by inducing cell detachment. Moreover, the expression of VE-cadherin and F-actin formation showed a reorganization of the cell structure within 2 h of 1 mM Omegaven addition. Interestingly, the study's findings contradict previous studies and revealed that Omegaven at high concentration, but not Intralipid, induces cell detachments, impairing endothelial cells' barrier function. In summary, our studies shed new light on the effect of lipid emulsions on the endothelium.
脂肪乳剂对于救命的全胃肠外营养（TPN）至关重要。它们的组成提供了大量的必需脂肪酸和热量，为数百万患有严重疾病的患者提供了支持。然而，超过 90%的患者报告了几种 TPN 介导的副作用。本项目旨在研究大量ω3 脂肪酸（Omegaven）乳剂与大量ω6 脂肪酸（Intralipid）乳剂对内皮屏障功能的影响。EA.hy926 细胞系进行培养和孵育，并用 0.01、0.1 和 1 mM 脂肪乳剂处理。使用 ECIS 技术、免疫荧光显微镜、流式细胞术进行的活力测量、多重细胞因子分析和 qRT-PCR 评估这些脂肪乳剂对屏障功能的影响。BODIPY 染色证实了内皮细胞对脂肪酸的摄取。ECIS 测量表明，高浓度的 Omegaven 通过诱导细胞脱落来防止屏障形成并损害屏障功能。此外，VE-钙粘蛋白的表达和 F-肌动蛋白的形成显示出细胞结构在 1 mM Omegaven 添加后 2 小时内的重新组织。有趣的是，该研究的发现与之前的研究相矛盾，表明高浓度的 Omegaven 而不是 Intralipid 诱导细胞脱落，损害内皮细胞的屏障功能。总之，我们的研究揭示了脂肪乳剂对内皮的影响的新视角。
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