Abstract
Critical leg ischemia (CLI) complicated by diabetes mellitus (DM), which is a very common and dangerous disease, represents the ultimate stage of peripheral arterial disease. Patients are treated with antiplatelet drugs, statins and limb revascularization, but a significant number of patients are not candidate for revascularization. Literature shows that in such cases, gene therapy could be a perfect therapeutic option. The aim of our study was to evaluate efficacy of double vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) gene therapy in patients with CLI complicated by DM. We observed that 90 days after administration, serum level of VEGF and ankle-brachial index increased significantly (p < 0.001) and rest pain decreased significantly compared with the control group (p < 0.002). Moreover considerable improvement in vascularization was observed in computed tomography angiography (P = 0.04). Based on the results of this study, we suggest that the therapy with pIRES/VEGF165/HGF bicistronic plasmid administration is a safe and effective method of treatment of patients with both CLI and DM.Graphical abstract
Highlights
Critical leg ischemia (CLI) indicates the final stage of peripheral arterial disease (PAD)
Due to the fact that CLI is most commonly caused by atherosclerosis obliterans, it is heavily associated with smoking and diabetes mellitus (DM) [5, 6, 17]
Based on previous studies and the fact that angiogenesis is a complicated process that requires many proangiogenic factors for proper vessel formation, we have developed bicistronic vectors carrying plasmid of the internal ribosome entry site pIRES/VEGF165/hepatocyte growth factor (HGF) encoding human VEGF165 and HGF, which is a novel therapy of CLI and DM based on dual gen construction
Summary
Critical leg ischemia (CLI) indicates the final stage of peripheral arterial disease (PAD). Because there is no directly CLI aimed medication, the only cure for “not candidate for revascularisation” (NCR) patients is oral antiplatelet drugs, statins, treatment of DM and smoking cessation This patients’ cohort has a poor prognosis, including a 1 year amputation rate of 40% and a mortality as high as 20% [4,5,6]. VEGF is the key factor in angiogenesis by stimulating the proliferation and migration of endothelial cells, which leads to the formation of new vessels This process requires the presence of other growth factors such as HGF [2, 10, 20, 25, 27]. A way to bypass these obstacles is to use plasmid coding cytokines
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