title: Endothelial cells are highly heterogeneous at the level of cytokine-induced insulin resistance.
abstract: The endothelial wall plays a crucial role in various diseases as it serves as the barrier between circulatory system and organ tissue. Inflammation-driven insulin resistance and subsequent endothelial dysfunction represent a pathomechanism in cardiovascular diseases such as atherosclerosis and myocardial infarction. It was recently suggested that insulin resistance also contributes to the pathogenesis of psoriasis, a chronic inflammatory disease of the skin. However, it is not clear whether similar mechanisms at the endothelium contribute to the disease. In this study, we ask which endothelial cells are most suitable to address this question. We investigated the insulin response of four cell types (primary cells and cell lines) representing different vascular beds (micro- and macrovascular cells) in the presence of different pro-inflammatory cytokines. All four cell types used responded well to insulin; however, the ability to become resistant to insulin due to an inflammatory stimulus by cytokines involved in psoriasis (e.g. IL-1β, IL-12, IL-17, IL-23 and TNF-α) was very heterogeneous and could not be attributed to the differential expression of the cognate cytokine receptors. We conclude that this disparity is due to the different origins and properties of the endothelial cells used. Thus, endothelial cells should be carefully selected for the purpose of the respective study, particularly when it comes to analysing the pathogenesis of a disease and the search of new molecular targets for innovative therapies.
authors.affiliation: Department of Dermatology, Clinic of the Goethe University, Frankfurt am Main, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Woth
authors.forename: Claudia
authors.initials: C
authors.lastname: Prein
authors.forename: Katja
authors.initials: K
authors.lastname: Steinhorst
authors.forename: Sandra
authors.initials: S
authors.lastname: Diehl
authors.forename: Wolf-Henning
authors.initials: WH
authors.lastname: Boehncke
authors.forename: Claudia
authors.initials: C
authors.lastname: Buerger
mesh_terms: D001921:Brain / Q000166:cytology; D002460:Cell Line; D002461:Cell Line, Transformed; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D007333:Insulin Resistance / Q000502:physiology*; D008833:Microcirculation; D010641:Phenotype; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D011565:Psoriasis / Q000276:immunology*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology
chemical_list: D016207:Cytokines
keywords: cytokines; endothelial cells; heterogeneity; insulin resistance; psoriasis