Efficacy of therapeutic angiogenesis in patients with chronic lower limb ischemia

Abstract

Therapeutic angiogenesis is a promising treatmentmodality in patients with chronic lower limb ischemia, forwhom revascularization is not indicated. A number of studiesdemonstrated satisfactory therapeutic effects of gene andcell-based therapy targeted to stimulate angiogenesis. At thesame time the factors affecting the efficacy of angiogenesisstimulation in clinical settings are under-investigated.In the given study 30 patients, aged 49-78 years withchronic lower limb ischemia of atherosclerotic origin (FontaineIIb-IV) were randomized into groups of gene therapy (GT) orthe control group (C). Plasmid DNA containing an encodingpart of the vascular endothelial growth factor (VEGF-165)gene was inserted into ischemic limb muscles of the GTpatients. All the patients had sessions of treadmill trainingwalking. Besides clinical findings, angiography, scintigraphy,transcutaneous oxymetry, laser Doppler examination, duplexultrasonography, treadmill test were carried out to evaluatethe invention efficacy. Also circulating progenitor cell countwas assessed by flow cytometry, ELISA was used to evaluateangiogenic growth factors. In 3 months limb perfusionrate, painless walking distance, collateral circulation indicesincreased. In 50% of patients the therapeutic effect wasassessed as moderate (Rutherford +2), in 30% as minimal(Rutherford +1), 20% of patients showed no dynamics.Clinical laboratory tests had no significant dynamics in thegroup of standard therapy. No serious complications werenoted. In a correlation test the efficacy of angiogenic therapywas associated with a patent ileac segment, shorter smokinghistory and higher ankle-brachial index.

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