title: Differential impact of oleate, palmitate, and adipokines on expression of NF-κB target genes in human vascular smooth muscle cells.
abstract: It is widely accepted that obesity is a major risk factor for the development of atherosclerosis. In this context, adipose tissue produces a variety of adipokines and releases free fatty acids, contributing to a chronic-low grade inflammation state implicated in vascular complications. In this study, we investigated the role of adipokines, oleic acid (OA), palmitic acid (PA), and the combinations on activation of NF-κB target genes in human vascular smooth muscle cells (SMC) to assess the hypothesis of synergistic interactions between these molecules. Adipocyte-conditioned medium (CM), generated from human adipocytes, in combination with low concentrations of OA, but not PA, induces SMC proliferation and activation of the transcription factor NF-κB in a synergistic way. Combined treatment of CM and OA further regulates a set of downstream NF-κB target genes including angiopoietin-1, activin A, and MMP-1, all critically involved in SMC dysfunction. This suggests that the lipotoxic potential of fatty acids is substantially enhanced by the presence of adipocyte-derived factors.
authors: Paul-Langerhans-Group, Integrative Physiology, German Diabetes Center, Düsseldorf, Germany.
authors: Daniela
authors: D
authors: Lamers
authors: Raphaela
authors: R
authors: Schlich
authors: Angelika
authors: A
authors: Horrighs
authors: Andrea
authors: A
authors: Cramer
authors: Henrike
authors: H
authors: Sell
authors: Juergen
authors: J
authors: Eckel
mesh_terms: D028341:Activins / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism; D054392:Adipokines / Q000494:pharmacology / Q000502:physiology*; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D017077:Culture Media, Conditioned; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D019301:Oleic Acid / Q000494:pharmacology / Q000502:physiology*; D019308:Palmitic Acid / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology; D014657:Vasculitis / Q000378:metabolism / Q000473:pathology
chemical_list: D054392:Adipokines; D042682:Angiopoietins; D051017:Apoptosis Regulatory Proteins; C483024:CCL5 protein, human; C502539:CIDEA protein, human; D018946:Chemokine CCL5; D017077:Culture Media, Conditioned; C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C422405:activin A; D028341:Activins; D019301:Oleic Acid; D019308:Palmitic Acid; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1