Antioxidative und antiatherosklerotische Effekte von PETN — ein prognostisches Desiderat

  • Henning Schröder
  • Aida Abate
  • Stefanie Oberle-Plümpe
  • Phyllis A. Dennery
  • Hendrik J. Vreman
  • Heinz T. Schneider
  • Dirk Stalleicken

Zusammenfassung

Der NO-Donor Pentaerithrityltetranitrat (PETN*) besitzt als Langzeitnitrat antiischämische und vasodilatierende Wirkung. Außerdem induziert PETN antiatherogene und antioxidative Effekte, wobei die verantwortlichen zellulären Mechanismen bisher nicht geklärt werden konnten. Daher sind wir in verschiedenen Studien der Frage nachgegangen, ob PETN und sein Metabolit PETriN in der Lage sind, die Expression der antioxidativen Protein Ferritin und Hämoxygenase-1 (HO-1) zu modulieren. PETriN stimulierte sowohl die endotheliale Expression der HO-1 als auch die Bildung der HO-1-Metabolite Bilirubin und Kohlenmonoxid. Gleichzeitig führte die Inkubation von Endothelzellen mit PETriN zu einer deutlichen Stimulation der Ferritin-Expression. Nach Vorbehandlung mit PETriN war die Sensibilität von Endothelzellen gegenüber oxidativem Stress herabgesetzt. Dieser Effekt war vergleichbar mit der zellprotektiven Wirkung von exogen zugesetztem Bilirubin. Die Langzeitnitrate Isosorbiddinitrat (ISDN) und Isosorbidmononitrat (ISMN) zeigten unter diesen Bedingungen weder einen Effekt auf die Expression von HO-1 und Ferritin im Endothel noch eine signifikante Zellprotektion. Möglicherweise sind zur Aktivierung endogener antioxidativer Signalwege NO-Mengen erforderlich, die in diesem Zellkulturmodell von Mono- und Dinitraten erst in einem wesentlich höheren Konzentrationsbereich generiert werden. In Übereinstimmung mit diesen Beobachtungen haben tierexperimentelle Untersuchungen und Studien an menschlichen Probanden ergeben, dass der HO-1-Induktor PETN im Gegensatz zu anderen Langzeitnitraten die endotheliale Dysfunktion verbessert und atherosklerotische Gefäßveränderungen unterdrückt. Weitere klinische Studien werden nötig sein, um zu klären, ob PETN neben seiner positiven Wirkung auf die Angina-pectoris-Symptomatik auch die Progredienz der koronaren Herzkrankheit durch Aktivierung vasoprotektiver Signalwege kausal beeinflussen kann.

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Copyright information

© Steinkopff Verlag Darmstadt 2004

Authors and Affiliations

  • Henning Schröder
  • Aida Abate
  • Stefanie Oberle-Plümpe
  • Phyllis A. Dennery
  • Hendrik J. Vreman
  • Heinz T. Schneider
  • Dirk Stalleicken

There are no affiliations available

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