Zytokinbeschichtete Stents als neue Werkzeuge der angiogenen Therapie

Zusammenfassung

Die Stimulation des endogenen adaptiven Gefäßwachstums (Angiogenese, Arteriogenese) stellt einen vielversprechenden alternativen Therapieansatz zur Behandlung okklusiver Gefäßerkrankungen dar. Trotz der Vielzahl experimentell wirksamer Substanzen ist der erfolgreiche Transfer in den klinischen Gebrauch jedoch ausgeblieben. Als Hauptgrund für die beobachteten neutralen Effekte wird unter anderem die Art der Applikation angesehen. Obwohl präklinische Studien die Überlegenheit einer kontinuierlichen intraarteriellen Gabe gezeigt haben, wurde mangels technischer Machbarkeit in klinischen Studien auf Bolustherapie bzw. intravenöse oder subkutane Applikation ausgewichen. Die Fortschritte in der Entwicklung der ˶drug eluting stents“ eröffnen neue Möglichkeiten der lokalen Medikamentenfreisetzung, insbesondere im Koronarstromgebiet. Die Abgabe von Wachstumsfaktoren wie TGF-beta von solchen Stents ließ sich experimentell bereits zur Stimulation des Kollateralwachstums nutzen. Ein solcher Ansatz wird in Zukunft weitere Möglichkeiten der ortbegrenzten Therapie schaffen und z. B. die gezielte Stabilisierung atherosklerotischer Plaques ermöglichen.

Summary

The stimulation of the endogenous adaptive vessel growth (angiogenesis, arteriogenesis) provides a promising therapeutic approach for the large number of patients with vascular occlusive disease that is not eligible for current interventional treatments. Despite the proven efficacy of various factors in pre-clinical experimental studies, the successful translation of angiogenic therapies into clinical practice yet remains to be made. Most authors identified the mode of administrations as culprit for the neutral effects observed in the majority of clinical trials. Although experimental studies have proven the superiority of continuous intra-arterial application above other routes (iv, im, sc), clinical trials focused on either bolus therapy, iv or sc application respectively, due to the lack of technical solutions to fulfill the requirements of intra-arterial delivery. The recent developments in the field of drug eluting stents may offer new possibilities for local drug delivery. Local release of cytokines, such as TGF-beta, has been shown to induce collateral growth in an experimental model of PAD. Other factors might eventually render useful to stabilize atherosclerotic plaques downstream of the site of stent implantation.

Schlüsselwörter

Beschichtete Stents - Angiogenese - Arteriogenese - Applikation von Medikamenten - Zytokine

Keywords

Drug-eluting stents - angiogenesis - arteriogenesis - drug delivery - cytokines

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