Gene therapy of cardiovascular diseases
Languages of publication
Despite progress in pharmacotherapy, there is still a lack of efficient treatment of advanced stages of cardiovascular diseases. Therefore, great expectations are connected with gene therapy. First clinical experiments of gene transfer of vascular endothelial growth factor (VEGF) were carried out in 1994-1998 on patients with critical leg ischemia. They resulted in the improvement of vascularisation and prevented the amputation of the limbs. Promising results have been also obtained with DNA decoys binding the EF2 transcription factor. In this way, the expression of genes enhancing the proliferation of vascular smooth muscle cells have been inhibited and in consequence the narrowing of the lumen of arterio-venous bypasses have been inhibited. Moreover, the experimental data from animal models of cardiovascular diseases suggest that the improvement patients' conditions of can be obtained by the transfer of genes modulating the inflammatory processes which are the main underlying cause of atherosclerosis. Thus, the enhanced expression of heme oxygenase-1, nitric oxide synthases or superoxide dismutases may beneficially influence the functions of the vessels. This protective activity may involve moderate enhancement of the synthesis of VEGF. Owing to this, the improvement of angiogenesis can be obtained without the risk of side effects associated with very high, unregulated expression of this growth factor. Further progress in gene therapy of cardiovascular diseases will depend on the results of clinical trials, investigations of the mechanisms of disturbance in gene expression associated with cardiovascular diseases, as well as on the development of efficient methods of targeted delivery and regulation of the expression of therapeutic genes.
Publication order reference
Jozef Dulak, Zaklad Biochemii Komorki, Wydzial Biotechnologii, Uniwersytet Jagiellonski, ul. Gronostajowa 7, 30-387 Krakow, Poland