Damage to vascular endothelial cells by high insulin levels is associated with increased expression of ChemR23, and attenuated by PPAR-gamma agonist, rosiglitazone

OBJECTIVE: This study investigated the effect of different insulin concentrations on the activity of vascular endothelial cells (VECs), and the role of PPAR. activator rosiglitazone (RGZ) on the expression of the chemerin receptor, ChemR23, in insulin-treated human umbilical vein endothelial cells (HUVECs). METHODS: Cell viability was determined in HUVECs treated with different insulin concentrations. Immunofluorescence staining was used to detect ChemR23 expression in insulin-treated HUVECs. Western blot assays were used to evaluate ChemR23 and PPAR gamma protein expression in insulin-treated HUVECs after pretreatment with PPAR gamma activator (RGZ) or inhibitor (GW9662). RESULTS: High insulin concentrations significantly inhibited HUVEC cell viability compared to low insulin concentrations, and this inhibition was attenuated by pretreatment with RGZ. High concentrations of insulin caused a significant upregulation of ChemR23 and a significant downregulation of PPAR gamma. These effects were attenuated by RGZ pretreatment, while PPAR gamma antagonist, GW9662 reversed this attenuation. CONCLUSION: ChemR23 upregulation may play a role in VEC damage caused by high concentrations of insulin. The protective effect of PPAR gamma activation in VECs may be mediated via ChemR23 downregulation.