Fan Xiao1,2, Xin Li1, Juan Wang1, Jie Cao3. 1. Department of Respiratory and Critical Care, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. 2. Department of Respiratory Medicine, Tianjin Third Central Hospital - Branch Hospital, 220 Jiangdu Road, Hebei District, Tianjin, 300250, China. 3. Department of Respiratory and Critical Care, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. tjzyyhxkcj@163.com.
Abstract
BACKGROUND: Hypoxia induces vascular endothelial injuries; however, the mechanisms involved and effects of interventions remain unclear. OBJECTIVE: Investigate the inflammatory response and oxidative stress in co-cultured neutrophils and vascular endothelial cells, apoptotic changes in endothelial cells, and effects of the antioxidant, Tempol, or the NF-êB inflammatory channel blocker, pyrrolidine dithiocarbamate (PDTC), upon endothelial cells under conditions of intermittent and/or continuous hypoxic exposure. 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 8 h. 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-α, IL-6, ICAM-1, and 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. Bcl-x1 expression and Bcl-x1/BAK ratios were decreased and BAX increased in the OS versus IH, CH, OS+T, or 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.
BACKGROUND:Hypoxia induces vascular endothelial injuries; however, the mechanisms involved and effects of interventions remain unclear. OBJECTIVE: Investigate the inflammatory response and oxidative stress in co-cultured neutrophils and vascular endothelial cells, apoptotic changes in endothelial cells, and effects of the antioxidant, Tempol, or the NF-êB inflammatory channel blocker, pyrrolidine dithiocarbamate (PDTC), upon endothelial cells under conditions of intermittent and/or continuous hypoxic exposure. 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 8 h. 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-α, IL-6, ICAM-1, and 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. Bcl-x1 expression and Bcl-x1/BAK ratios were decreased and BAX increased in the OS versus IH, CH, OS+T, or 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.
Authors: Mathias Grebe; Hans Joachim Eisele; Norbert Weissmann; Christian Schaefer; Harald Tillmanns; Werner Seeger; Richard Schulz Journal: Am J Respir Crit Care Med Date: 2006-01-26 Impact factor: 21.405
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