Impact of Unsaturated Fatty Acids on Cytokine-Driven Endothelial Cell Dysfunction

Abstract

Polyunsaturated fatty acids (PUFA) are reported to exert prophylactic and acute therapeutic effects in diseases linked to endothelial dysfunction. In the present study, the consequences of a PUFA enrichment of endothelial cells (cell line TIME) on cell viability, expression of the cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1), synthesis of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular adhesion molecule 1 (VCAM-1), and production of the coagulation factors plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and tissue factor (TF) was analyzed in parallel. PUFA of both the n3 and the n6 family were investigated in a physiologically relevant concentration of 15 µM, and experiments were performed in both the presence and the absence of the pro-inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Supplementation of the culture medium with particular fatty acids was found to have a promoting effect on cellular production of the cytokines IL-6, IL-8, GM-CSF, and MCP-1. Further on, PUFA treatment in the absence of a stimulant diminished the percentage of endothelial cells positive for ICAM-1, and adversely affected the stimulation-induced upregulation of VCAM-1. Cell viability and production of coagulation factors were not or only marginally affected by supplemented fatty acids. Altogether, the data indicate that PUFA of either family are only partially able to counterbalance the destructive consequences of an endothelial dysfunction.

Impact of Polyunsaturated Fatty Acids on miRNA Profiles of Monocytes/Macrophages and Endothelial Cells—A Pilot Study

“…It should be noted that, in our study, cellular miRNA profiles were measured as a function of long-term PUFA supplementation, which leads to an incorporation of the fatty acids into the plasma membrane. The periods of supplementation used in our experiments are already proved by us to result in a membrane fatty acid steady state [23,24]. From this perspective, our data hint toward an innovative mechanism of PUFA action.…”

Polyunsaturated Fatty Acids of Both the Omega-3 and the Omega-6 Family Abrogate the Cytokine-Induced Upregulation of miR-29a-3p by Endothelial Cells

“…A previous study of the working group on endothelial cells, which used identical cultivation, supplementation, and stimulation conditions as the present work, can serve as an example. Here, an inhibitory effect of AA on the cytokine-induced upregulation of the adhesion molecule VCAM-1 was found, an effect that had previously only been described for DHA and EPA [ 2 ]. Additionally, the effects of DHA and AA described in the present study also point consistently in the anti-inflammatory direction for both fatty acid families.…”

“…Endothelial cells play an important role in both acute and chronic inflammatory processes and can be directly activated by proinflammatory cytokines [ 1 , 2 ]. In the activated state, endothelial cells are characterized by the production of reactive oxygen and nitrogen intermediates as well as proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP-1), and the interleukins IL-1β, IL-6, and IL-8 [ 1 , 2 ]. What is more, coagulation processes are facilitated and leukocyte adhesion and extravasation are promoted [ 1 , 2 ].…”

“…In the activated state, endothelial cells are characterized by the production of reactive oxygen and nitrogen intermediates as well as proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP-1), and the interleukins IL-1β, IL-6, and IL-8 [ 1 , 2 ]. What is more, coagulation processes are facilitated and leukocyte adhesion and extravasation are promoted [ 1 , 2 ]. Accordingly, endothelial cells are regarded as part of a functional immune defense actively participating in the combat of invading pathogens.…”

“…Investigations by our working group have already shown that the cytokine-driven activation of endothelial cells is modulated by unsaturated fatty acids [ 2 ]. In line with this, PUFAs are already used in clinical practice to accompany the therapy of inflammatory diseases.…”