Abstract

The present study focuses on the application of a therapeutic strategy in patients with chronic severe lower limb ischaemia using a plasmid vector encoding the vascular endothelial growth factor (phVEGF165). It has been shown that VEGF promotes neo-vascularization and blood vessel network formation and thus might have the ability to improve blood-flow at the level of the affected limbs. However, little information is available regarding the necessary level of expression of VEGF and its possible related adverse effects. We have subcloned VEGF 165isoform into pCMV-Script expression vector (Stratagene) under the control of the CMV promoter. Three patients with chronic ischaemia of the lower limb, considered as not suitable for surgical re-vascularization, received intramuscular injection with 0.5 ml saline solution containing 1011 copies of VEGF 165 plasmid. The clinical evolution has been monitored by angiography and estimated by walking time on the rolling carpet (Gardner protocol). Two months after therapy, all three patients showed complete relief of rest pain, improvement of ischaemic ulcer lesions and increased walking distance on the rolling carpet most probably due to appearance of newly formed collateral vessels.

Highlights

  • Cardiovascular disease represents a major cause of morbidity and mortality worldwide with atherosclerosis being one of the main pathological mechanism involved

  • The present study evaluates the clinical outcome and angiographically assesses the formation of new blood vessels after VEGF165 gene therapy in patients with severe chronic lower limb ischaemia

  • We designed a single blind study aiming at analysing the possible effect of VEGF165 muscle overexpression on the clinical evolution of the patients diagnosed with lower limb severe chronic ischaemia unresponsive to classical treatment

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Summary

Introduction

Cardiovascular disease represents a major cause of morbidity and mortality worldwide with atherosclerosis being one of the main pathological mechanism involved. Previous studies have shown a strong relationship between atherosclerosis promoting factors (high blood pressure, diabetes mellitus, smoking, hyperlipidemia, sedentariness) and the development of the peripheral ischaemic disease (Brown et al 1972; Helmlinger et al 2000). This condition affects mainly the arteries of the lower limb leading to decreased blood flow with subsequent ischaemic lesions. Severe lower limb ischaemia accounts for 70% of the 150 million lower limb amputations (Eskelinen et al 2004). Conventional treatment of lower limb ischaemia has two main components: conservative and interventional/surgical therapy.

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