Mechanisms of vascular endothelial cell injury in response to intermittent and continuous hypoxia exposure and protective effects of anti-inflammatory and anti-oxidant agents

Abstract

Objective: To investigate the mechanism of vascular endothelial cell injury and the anti-inflammatory and anti-oxidative intervention measures of neutrophil and endothelial cells in intermittent and continuous hypoxic exposure at the cellular level. Methods: Polymorphonuclear neutrophils co-cultured with human umbilical vein endothelial cells were subjected to the following conditions: intermittent normoxia (IN), intermittent hypoxia (IH), continuous hypoxia (CH), intermittent with continuous hypoxia (OS), OS + Tempol (OS+T), or OS + PDTC (OS + P) for 2, 5 or 8h. Inflammatory factors, TNF-α and IL-6, the adhesion molecule, ICAM-1, CAT activity and MDA concentrations in supernatants from the co-culture as well as pro- (Bak) and anti- (Bcl-xl) apoptotic gene expression levels in the endothelial cells were determined. Results: Inflammatory factors, adhesion molecules, oxidative stress and apoptosis genes in all groups showed significant, time-dependent increases as compared with the IN group. TNF-a, IL-6, ICAM-1, MDA levels in the OS group were increased while CAT was decreased as compared with that observed in the IH, CH, OS+T and OS+P groups. Both pro- and anti-apoptotic proteins showed time dependent increases, while the Bcl-x1/BAK ratio decreased over these times. Tempol and PDTC partially prevented these effects. Conclusion: Inflammation, oxidative stress and apoptosis are all involved in vascular endothelial injury induced by OS. Anti-inflammatory and anti-oxidative interventions can partially improve effects of OS.