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Mechanismen der arteriellen Restenose und Therapieansätze zur Prävention

Mechanisms of arterial restenosis and treatment strategies for its prevention

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Zusammenfassung

Sowohl gefäßchirurgische als auch endovaskuläre Interventionen bedingen ein Trauma der Gefäßwand, insbesondere des Endothels. Die Reaktion des Gefäßes, die sich in konstriktivem Remodelling und Neointimabildung äußert, ist weiterhin der limitierende Faktor kurativer Eingriffe. Das Einbringen von Stents verhindert zwar das konstriktive Remodelling, verstärkt aber die Bildung von Neointima, die hauptverantwortlich für die In-Stent-Restenosen ist. Neointima bildet sich als Reaktion auf Thrombosierung, lokale Entzündung und medio-intimale Verletzungen nach Ballondilatation im Bereich arterieller Anastomosen oder Fogarty-Manöver. Derzeit konzentriert sich die Prävention der Restenose auf die Reduzierung der Neointimabildung durch beschichtete Stents, deren Vorreiter die Taxus- und Cypherstents darstellen. Daneben sind weitere experimentelle Ansätze aktuell Gegenstand der Forschung, um neue Therapieansätze zu etablieren und das Problem von Neointimabildung, Thrombose und konstriktivem Remodelling zu lösen. Dazu zählen neben lokaler und systemischer Pharmakotherapie, Brachy- und Lasertherapie auch gentherapeutische Ansätze, die aktuell in experimentellen und ersten klinischen Studien untersucht werden. Die selektive, gleichzeitige, eventuell sogar polyphasische Regulation verschiedener, an der Restenoseentwicklung beteiligter Gene könnte in Zukunft eine weitere Optimierung der Restenoseprävention ermöglichen.

Abstract

Both vascular surgery and endovascular interventions traumatise the arterial wall, especially the endothelium. The vessel responds with neointimal hyperplasia and/or constrictive remodelling, and this is still the limiting factor in curative interventions. Stent placement prevents constrictive remodelling but is the main trigger for in-stent restenosis. Hyperproliferation of neointimal tissue is the main response to arterial thrombosis, local inflammation or medio-intimal injury such as occurs, for example, after balloon dilatation in the region of arterial anastomoses or of a thrombectomy (Fogarty-manoeuvre). At present, research on prevention of restenosis is focused on inhibiting neointimal hyperproliferation by using drug-eluting stents, and especially sirolimus- or paclitaxel-eluting stents. In addition, further experimental research work is in progress, with the aim of esablishing new treatment regimens and solving the problem of neointimal formation, thrombosis and constrictive remodelling. These include both local and systemic pharmacological therapy, brachy- and laser therapy, and many genetic treatment options, some of which are currently the subjects of experimental studies and early-stage clinical trials. Gene therapy seems like a promising way of preventing restenosis, but has not yet been tested in clinical trials. In the near future, selective, simultaneous, and perhaps even polyphasic regulation for gene silencing of two or more genes involved in the development of restenosis could improve the long-term patency rate.

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  1. Chirurgische Klinik und Poliklinik Großhadern, Klinikum der Universität München, Marchinoninistraße 15, 81377, München, Deutschland

    A. Kühnl, K.-W. Jauch & R. Kopp

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  1. A. Kühnl
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  2. K.-W. Jauch
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  3. R. Kopp
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Correspondence to A. Kühnl.

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Kühnl, A., Jauch, KW. & Kopp, R. Mechanismen der arteriellen Restenose und Therapieansätze zur Prävention. Gefässchirurgie 11, 347–355 (2006). https://doi.org/10.1007/s00772-006-0481-0

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