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Therapeutisches Potenzial der Stickstoffmonoxid-Synthase-Isoformen in Restenose, Transplantat- und Bypassarteriosklerose

Therapeutic potential of nitric oxide synthase isoforms in restenosis, transplantation and bypass atherosclerosis

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Zusammenfassung

Die verschiedenen biologischen Effekte von Stickstoffmonoxid (NO) haben zu einer intensiven Erforschung der Rolle von NO in der Physiologie und Pathophysiologie von Gefäßerkrankungen geführt. Durch Zuhilfenahme von rekombinanter DNA und Gentransfer konnte der Effekt der endogenen NO-Produktion durch die Familie der NO-Synthase-Enzyme (NOS) in unterschiedlichen Geweben untersucht werden. Die Umsetzbarkeit einer vaskulären NOS-Gentherapie konnte in Tiermodellen gut demonstriert werden. Vor einer möglichen Anwendung der NOS-Gentherapie sollten allerdings aktuelle technische Limitationen und Sicherheitsrisiken genauer evaluiert werden. Da bekannt ist, das NO einen erheblichen Einfluss auf die spontane Arterioskleroseentwicklung, die Restenose nach Angioplastie, die Arterioskleroseentwicklung in Transplantatvenen und Transplantatarterien sowie die kardiale Allotransplantvaskulopathie hat, soll dieser Artikel den aktuellen Stand der Forschung mit besonderem Augenmerk auf die potenziellen Möglichkeiten einer NOS modulierenden Therapie zusammenfassen.

Abstract

The diverse biological effects of nitric oxide (NO) have led to intense research into its roles in vascular physiology and pathophysiology. Using recombinant DNA and gene transfer the effects of endogenous NO production by the family of NO synthase (NOS) enzymes can be elegantly studied in a variety of tissues. In addition, the feasibility of vascular NOS gene therapy has been demonstrated in animal models. However, technical and safety limitations have to be addressed before NOS gene therapy for cardiovascular disease is available for humans. Since NO exerts critical functions in vascular pathology, including atherosclerosis, post-angioplasty restenosis, vein graft atherosclerosis, transplant atherosclerosis and cardiac allograft vasculopathy, this article reviews recent progress in the field with a focus on potential future applications of NOS-modulating therapies.

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  1. Abteilung für Angiologie - Gefäßzentrum - Standort Innenstadt, Ludwig-Maximilians-Universität, Pettenkofer Str. 8a, 80336, München, Deutschland

    P.J. Kuhlencordt

  2. Medizinische Klinik I/Herz-Kreislaufzentrum, Universität Würzburg, Würzburg, Deutschland

    P. Padmapriya &  P.J. Kuhlencordt

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  1. P. Padmapriya
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Padmapriya, P., Kuhlencordt, P. Therapeutisches Potenzial der Stickstoffmonoxid-Synthase-Isoformen in Restenose, Transplantat- und Bypassarteriosklerose. Gefässchirurgie 14, 108–117 (2009). https://doi.org/10.1007/s00772-008-0668-7

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