The ATP Receptors P2X7 and P2X4 Modulate High Glucose and Palmitate-Induced Inflammatory Responses in Endothelial Cells

摘要: Endothelial cells lining the blood vessels are principal players in vascular inflammatory responses. Dysregulation of endothelial cell function caused by hyperglycemia, dyslipidemia, and hyperinsulinemia often result impaired vasoregulation, oxidative stress, inflammation, altered barrier function. Various stressors including high glucose stimulate release nucleotides thus initiating signaling via purinergic receptors. However, modulation responses palmitate remains unclear. In present study, we investigated whether effect is mediated P2X7 P2X4 if they play a role dysfunction. Transcript protein levels genes as well reactive oxygen species production, endothelial-leukocyte adhesion, permeability were human umbilical vein exposed to palmitate. We report increase extracellular ATP, expression P2X4, markers. Both antagonists inhibited palmitate-induced interleukin-6 with former having significant on interleukin-8 cyclooxygenase-2. The was confirmed siRNA knockdown addition, both decrease nitric oxide synthase. Blocking intercellular adhesion molecule-1 leukocyte-endothelial adhesion. Interestingly, enhanced that dependent P2X4. Furthermore, antagonizing palmitate-mediated activation p38-mitogen activated kinase. These findings support novel for coupled induction molecules modulating