title: Secretory products from human adipocytes impair endothelial function via nuclear factor kappaB.
abstract: Hyperplasia and hypertrophy of fat cells can be found in obesity, and increased adiposity is associated with endothelial dysfunction as an early event of atherosclerosis. However, it is unclear whether human adipocytes directly influence endothelial function. To study the crosstalk between fat and endothelial cells, human umbilical venous endothelial cells (HUVECs), and human coronary artery endothelial cells (HCAECs) were cultured in infranatants (Adipo) of primary differentiated human adipocytes. Interestingly, incubation of HUVECs and HCAECs with Adipo significantly increased monocyte adhesion 7.3 and 2.2-fold, respectively. VCAM-1, ICAM-1, and E-selectin in HUVECs were upregulated 3.9, 3.0, and 9.5-fold, respectively, under these conditions. Furthermore, Adipo significantly stimulated NFkappaB activity 1.9-fold. The NFkappaB inhibitor MG-132 and heat inactivation significantly reversed Adipo-stimulated monocyte adhesion. TNFalpha-neutralizing antibodies partly reversed Adipo-induced monocyte adhesion. In contrast, thiazolidinedione-pretreatment of human adipocytes did not alter the effects of Adipo. Adipo did not show cytotoxic effects. Taken together, we demonstrate that endothelial dysfunction is induced by adipocyte-secreted factors via NFkappaB partly dependent on TNFalpha.
authors.affiliation: University of Leipzig, Department of Internal Medicine III, 04103 Leipzig, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: Kralisch
authors.forename: Grit
authors.initials: G
authors.lastname: Sommer
authors.forename: Verena
authors.initials: V
authors.lastname: Stangl
authors.forename: Uwe
authors.initials: U
authors.lastname: Köhler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Holger
authors.initials: H
authors.lastname: Stepan
authors.forename: Renaldo
authors.initials: R
authors.lastname: Faber
authors.forename: Andreas
authors.initials: A
authors.lastname: Schubert
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lössner
authors.forename: Angelika
authors.initials: A
authors.lastname: Vietzke
authors.forename: Matthias
authors.initials: M
authors.lastname: Bluher
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Mathias
authors.initials: M
authors.lastname: Fasshauer
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D054392:Adipokines / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D020738:Leptin / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D016328:NF-kappa B / Q000502:physiology*; D052243:Resistin / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D054392:Adipokines; D019040:E-Selectin; D020738:Leptin; D007976:Leupeptins; D016328:NF-kappa B; D052243:Resistin; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde