Angiogenic Gene Therapy With Vascular Endothelial Growth Factor – Hope or Hype?
Angiogenetische Gentherapie mit „Vascular Endothelial Growth Factor”–Hoffnung oder Illusion?
J. Dulak
From the 1 Department of Cell Biochemistry, Institute of Molecular Biology, Jagiellonian University, Krakow, Poland, the 2 Division of Cardiology, University of Innsbruck, and the 3 Division of Vascular Surgery, Department of Surgery, University of Vienna
Search for more papers by this authorAlicja Jozkowicz
From the 1 Department of Cell Biochemistry, Institute of Molecular Biology, Jagiellonian University, Krakow, Poland, the 2 Division of Cardiology, University of Innsbruck, and the 3 Division of Vascular Surgery, Department of Surgery, University of Vienna
Search for more papers by this authorJ. Dulak
From the 1 Department of Cell Biochemistry, Institute of Molecular Biology, Jagiellonian University, Krakow, Poland, the 2 Division of Cardiology, University of Innsbruck, and the 3 Division of Vascular Surgery, Department of Surgery, University of Vienna
Search for more papers by this authorAlicja Jozkowicz
From the 1 Department of Cell Biochemistry, Institute of Molecular Biology, Jagiellonian University, Krakow, Poland, the 2 Division of Cardiology, University of Innsbruck, and the 3 Division of Vascular Surgery, Department of Surgery, University of Vienna
Search for more papers by this authorAbstract
enSummary: Background: Angiogenesis is a promising novel therapeutic strategy to provide new venues for blood flow in patients with severe ischaemic heart and peripheral vascular diseases. Among several stimulators, the vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2, basic FGF) have been most widely studied. Methods: Preclinical animal studies suggested the strong therapeutic potentials of VEGF, and such positive effects have also been confirmed in a limited number of phase I clinical trials. However, some animal studies suggest the existence of a considerable risk associated with angiogenic therapy. Results: VEGF is strongly expressed in human atherosclerotic plaques, it promotes atherosclerosis in animal models, and there is evidence indicating that the plaque growth is dependent on the formation of new blood vessels. Therefore, for a convincing demonstration of the safety and efficacy of VEGF gene therapy, the clinical effects need to be evaluated in larger randomized, double-blinded clinical trials. Conclusions: Further understanding of the mechanisms of activity of angiogenic growth factors and the formation of blood vessels is required, and improved gene transfer methods are necessary to introduce therapeutic angiogenesis in clinical practice.
Abstract
deZusammenfassung: Grundlagen: Die Angiogenese ist eine vielversprechende neue therapeutische Strategie bei Patienten mit Myokardischämie und peripheren Gefäßerkrankungen. Unter den verschiedensten Stimulatoren sind der Vascular Endothelial Growth Factor (VEGF) und der Fibroblast Growth Factor-2 (FGF-2, basic FGF) am besten erforscht. Methodik: Vorklinische Tierversuche lassen ein großes therapeutisches Potential erwarten, und diese positiven Effekte werden von einer begrenzten Zahl von Phase-I-Studien bestätigt. Einige der experimentellen Studien lassen erhebliche Risiken in Verbindung mit einer angiogenetischen Therapie vermuten. Ergebnisse: VEGF wird von humanen atherosklerotischen Plaques verstärkt gebildet, fördert Atherosklerose am Tiermodell, und es gibt Anzeichen, daß das Plaquewachstum von der Bildung neuer Blutgefäße abhängig ist. Daher sollten die klinischen Effekte, um die Sicherheit und Effizienz einer VEGF-Gentherapie zu zeigen, in großen, randomisierten, doppelblinden, klinischen Studien evaluiert werden. Schlußfolgerungen: Um eine therapeutische Angiogenese in der klinischen Praxis anwenden zu können, ist ein genaueres Verständnis der Mechanismen der Aktivität von angiogenetischen Wachstumsfaktoren und der Bildung von Blutgefäßen und die Verbesserung der Gentransfermethoden nötig.
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