Insulin Resistance May Contribute to Upregulation of Adhesion Molecules on Endothelial Cells in Psoriatic Plaques

Abstract

Psoriasis primarily affects the skin, but also has a systemic dimension and is associated with severe comorbidities. Since endothelial cells play an important role in psoriasis as well as in the development of cardiovascular comorbidities, we investigated whether a common mechanism, namely cytokine-induced insulin resistance, underlies both pathologies. Activation of the insulin pathway was studied in psoriatic skin and dermal endothelial cells. Expression of adhesion molecules was assessed by flow cytometry, as well as their biological function in flow chamber experiments. The phosphorylation status of Akt, a central kinase in the insulin pathway, suggests that endothelial cells within psoriatic plaques are rendered insulin resistant by pro-inflammatory cytokines. Insulin counteracts the expression of adhesion molecules, but has limited effects on interactions between T cells and endothelial cells. Pro-inflammatory cytokines induce insulin resistance in endothelial cells, which may contribute to the development of the inflammatory infiltrate in psoriasis.

Impact of metabolic status on the incidence of psoriasis: a Korean nationwide cohort study

“…Second, insulin resistance may represent the link between the being metabolically obese and the pathogenesis of psoriasis, as increased insulin resistance is a key feature of obesity and metabolic disturbance 32 . Moreover, epidermal insulin resistance induced by proinflammatory cytokines has been reported to promote the persistent proliferation of keratinocytes 33 and endothelial dysfunction, and contribute to the development of psoriatic plaques 34 . Third, the oxidative stress from metabolic disturbance could be responsible for the pathogenesis of psoriasis, based on the increased reactive oxygen species burden and decreased antioxidant capacity in various stages of psoriasis 35 .…”

Peroxisome proliferator-activated receptor (PPAR) α and δ activators induce ICAM-1 expression in quiescent non stimulated endothelial cells

“…Adhesion was determined using Ibidi μ-slide VI chambers (Munich, Germany) [24]. Two days before treatment 1,8x10 5 HUVECs were seeded in each chamber.…”

Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with Gene Polymorphism Suggests a Role in Disease Pathogenesis

“…4E1, a monoclonal antibody against CD93 has been shown to inhibit angiogenesis, both in vitro and in vivo, without affecting endothelial cell survival (15). Previous studies suggest that the expression of CD93 on endothelial cells may also play a role in the regulation of cell adhesion and in the skin homing of inflammatory cells (10,16,17), which are important steps in initiating and maintaining inflammation in psoriasis (18).…”