Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: The role of poly(ADP-ribose) polymerase

L. Piconi, L. Quagliaro, R. Da Ros, R. Assaloni, D. Giugliano, K. Esposito, C. Szabó, Antonio Ceriello

Research output: Contribution to journalArticle

Abstract

It has been previously reported that endothelial cells exposed to constant high concentrations of glucose upregulate the expression of adhesion molecules. Moreover, it has been suggested that this phenomenon is related to generation of oxidative stress. It has also been suggested that oxidative injuries, related to high glucose, induce the activation of the enzyme poly ADP ribose polymerase (PARP), which can promote the expression of adhesion molecules and the generation of inflammation. Recent in-vivo and in-vitro evidence suggests that oscillation of glucose may play an autonomous and direct role in favoring the development of cardiovascular complications in diabetes. In this study we have investigated the effects of constantly high and intermittently high glucose on nitrotyrosine formation (a marker of nitrosative stress) and adhesion molecule (ICAM-1, VCAM-1 and E-selectin), as well as on interleukin (IL)-6 expression in human umbilical vein endothelial cells, either in the presence or in the absence of PJ34, a potent inhibitor of PARP. We found that oscillating glucose was more effective in triggering the generation of nitrotyrosine and inducing the expression of adhesion molecules and IL-6 than stable high glucose. Pharmacological inhibition of PARP suppressed both nitrotyrosine formation, adhesion molecule expression and IL-6 to the levels seen in the normal glucose conditions. Thus, PARP activation appears to be involved in both promoting nitrosative stress and upregulating adhesion molecules and inflammation in endothelial cells exposed to oscillating high glucose conditions.

Original languageEnglish
Pages (from-to)1453-1459
Number of pages7
JournalJournal of Thrombosis and Haemostasis
Volume2
Issue number8
DOIs
Publication statusPublished - Aug 2004

Keywords

  • E-selectin
  • ICAM-1
  • IL-6
  • Intermittent glucose
  • Poly (ADP-ribose) polymerase
  • VCAM-1

ASJC Scopus subject areas

  • Medicine(all)

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