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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 428363.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Fatty acids differentially influence phosphatidylinositol 3-kinase signal transduction in endothelial cells: impact on adhesion and apoptosis
Authors:Schaefer, M. B.; Wenzel, A.; Fischer, T.; Braun-Dullaeus, R. C.; Renner, F.; Dietrich, H.; Schaefer, C. A.; Seeger, W.; Mayer, K.
Date of Publication (YYYY-MM-DD):2008
Title of Journal:Atherosclerosis
Issue / Number:2
Start Page:630
End Page:637
Audience:Not Specified
Abstract / Description:In contrast to n-6 fatty acids like arachidonic acid (AA), the anti-inflammatory potential of n-3 fatty acids such as docosahexaenoic acid (DHA) has been demonstrated. We examined the phosphatidylinositol (PI)3-kinase dependent effects of AA versus DHA on monocyte rolling, adhesion and transmigration through inflammatory activated human umbilical venous endothelial cells (HUVEC) as well as on apoptosis, to investigate the impact on vascular inflammation. HUVEC were pre-incubated with AA, DHA or sham, and stimulated with VEGF, TNF-alpha or staurosporine. Rolling and adhesion were investigated by means of a parallel flow chamber; transmigration was performed in a static assay. Activation of PI3-kinase was measured as phosphorylation of protein kinase B (Akt). Apoptosis was determined by caspase-3 activity and annexin-V analysis. Pre-incubation of HUVEC with DHA markedly decreased TNF-alpha-induced monocyte rolling, adhesion, and transmigration, although expression of endothelial adhesion molecules was unchanged. In contrast, AA increased TNF-alpha-induced rolling. Both fatty acids did not alter TNF-alpha-mediated upregulation of the adhesion molecules ICAM-1, VCAM-1, and E-selectin. The divergent effects of AA and DHA were abrogated with PI3-kinase inhibitors. After pre-incubation with DHA, VEGF-, TNF-alpha- and staurosporine-induced phosphorylation of Akt was decreased when compared to AA. DHA pre-incubation significantly increased staurosporine-induced apoptosis. In addition, DHA in comparison to AA augmented staurosporine-mediated increase in caspase-3 activity. In conclusion, DHA-induced a reduction in rolling, adhesion and transmigration of monocytes through inflammatory activated HUVEC that is in part PI3-kinase dependent. PI3-kinase driven phosphorylation of Akt and apoptosis of HUVEC as contribution to the resolution of inflammation is differentially modulated by DHA versus AA.
Free Keywords:1-Phosphatidylinositol 3-Kinase/*physiology Apoptosis/physiology Arachidonic Acid/*pharmacology Cell Adhesion/immunology/physiology Cells, Cultured Docosahexaenoic Acids/*pharmacology *Endothelial Cells/immunology/physiology Humans Inflammation/*immunology Leukocyte Rolling/physiology Monocytes/*immunology Phosphorylation Signal Transduction/physiology Umbilical Veins/cytology
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
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