[Gene therapy with VEGF].
NEW THERAPEUTIC OPTION: Atherosclerosis-related conditions are the primary cause of mortality in western countries. The incidence of severe limb-threatening ischemia of the lower limbs reaches 500 to 1000 per million inhabitants. The lack of effective treatment capable of preventing amputation in the most severe cases has led to research into the development of collateral circulation to replace the occluded arteries. Preclinical data has demonstrated that angiogenic factors can stimulate collateral circulation. This new therapeutic approach is called "angiogenesis therapy". VEGF: Vascular endothelial growth factor (VEGF) is a DNA fragment coding for a protein that has raised great expectations which are now entering the era of reality. Several administration routes are possible. The DNA fragments can be deposited on the arterial wall using a catheter. The hydrogel balloon operates like an angioplasty balloon covered with a hydrophilic layer which delivers the DNA fragments when inflated. More recently, the intramuscular route has been used to take advantage of the vascular distribution of this angiogenic cytokine. The peripheral muscle cells can perform the transformation via transcription to a messenger RNA for translation into the human DNA protein. A real application of gene therapy.


CONCLUSIONS
Undeniable clinical benefit observed in the limited number of patients treated has led to proposing angiogenic cytokines for the treatment of ischemic heart disease when angioplasty or bypass surgery. The most recent series are small, but show that intramyocardial injection of VEGF is feasible. Larger randomized series will evaluate these techniques. Despite the large body of preclinical data, many questions remain unanswered.
Maillard
L
L
Laboratoire de Biotechnologie et Génétique expérimentale, CHU Trousseau, Tours. luc.maillard@med.univ-tours.fr
Peycher
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P
Fichaux
O
O
Vincentelli-Djeffal
D
D
D000818:Animals; D001161:Arteriosclerosis / Q000628:therapy*; D002417:Cattle; D003097:Collateral Circulation; D003327:Coronary Disease / Q000628:therapy*; D016207:Cytokines / Q000008:administration & dosage / Q000235:genetics; D053938:DNA Fragmentation; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D007866:Leg / Q000098:blood supply*; D008222:Lymphokines / Q000008:administration & dosage* / Q000235:genetics*; D018919:Neovascularization, Physiologic; D020033:Protein Isoforms; D011817:Rabbits; D015607:Stents; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016207:Cytokines; D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors