| Summary: | Vascular reconstruction remains a treatment of choice for critical limb ischemia. Bypass surgery has been accepted as the most effective therapy to achieve increase of blood flow and cure the ischemic symptoms. On the other hand, continuous increase of the patients suffering diabetes mellitus enhances the increase of the number of the patients with peripheral arterial disease (PAD). This tendency is also observed in Japan and expected to continue from now on. The reports of the Ministry of Health, Labor and Welfare of Japan indicated that more than 6% of population was treated for diabetes mellitus and more than 12% of population was supposed to be diabetic in 2002.1) This report also gave a warning for rapid and continuous increase of the diabetic patients at present and in the future.? As is well known, diabetes mellitus is one of the strong risk factors to cause an arteriosclerosis obliterans (ASO). Therefore, the patients with PAD will increase continuously and more severe ischemic limb will need to be treated. Moreover, diabetic macroangiopathy is characterized as showing diffuse stenosis and occlusion down to the foot arteries.2) Monckeberg’s medial calcification is also frequently observed in the ASO with diabetes mellitus.3) Therefore, along with the increase of the patients with PAD, the vascular reconstruction becomes technically demanding due to co-morbid diabetes with diffuse lesion and severe calcification. The patients, who show critical limb ischemia but are excluded from the operative candidate, are eventually performed major amputation. To prevent this disastrous sequel, therapeutic angiogenesis has been investigated.In 1996, Isner reported a new therapy to treat ischemic limb by using angiogenetic gene; vascular endothelial growth factor (VEGF).4) Since then, angiogenetic therapy started to be investigated by using gene transfer with VEGF, fibroblast growth factor (FGF)5) or hepatic growth factor (HGF).6) Animal study showed increase of the vascular network, disappearance of local coldness and recover of limb function.7,8) Human study also started by using these genes.? Major concern to use gene transfer is possible infection or carcinogenic effect via adenovirus which is used as a vector. To avoid this problem, plasmid is also used although the efficacy of transfer is less. The human application revealed that skin temperature increased, pain was cured and vascular network seemed to increase in angiography. However, the long-term effect remains undetermined.
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