Intermittent hypoxia-induced adipocyte derived secretory products cause inflammatory responses in endothelial cells in vitro

Obstructive sleep apnea is characterized by repetitive episodes of intermittent hypoxia (IH) which causes metabolic dysregulation in adipose tissues. The highly vascularized structure of adipose tissues enables the intercellular communication to the vascular endothelium. Activation of endothelium underlies the pathophysiology of endothelial dysfunction and initiates atherosclerosis. It is aimed to investigate the effect of IH on activation of human adipocytes, endothelial EA.hy926 cells (EA) and their interaction in vitro . Briefly, cultured adipocyte-subcutaneous and EA cells were exposed to IH (O 2 : 1% for 10 minutes alternating with 21% for 5 minutes) for 64 cycles. Some EA cells were incubated with conditioned medium derived from IH-treated adipocytes-subcutaneous (ADIPO). Levels of adiponectin, MCP-1 and IL6, catalase activity and proteins of interests were measured. IH caused significant release of inflammatory cytokines in adipocytes (MCP-1 and IL6) and EA cells (MCP-1) while adiponectin was downregulated in EA cells. Expression of endothelial nitric oxide synthase (eNOS) and catalase activity were reduced while cyclooxygenase-2, inducible NOS, p-Akt (ser473), p-Erk1/2 and p-p38 were increased in EA cells after exposure to IH. ADIPO-treated cells increased phosphorylation of p-Akt (ser473), p-Erk1/2 and p-NF-kB p65. IH induces inflammatory responses in adipocytes as well as endothelial cells with reduced catalase activity and eNOS in vitro . Comparable activation of inflammatory signalling pathways by IH and ADIPO is observed suggesting a regulatory role of adipocyte-derived secretory products after IH on endothelial functions.