Lower-extremity edema associated with gene transfer of naked DNA encoding vascular endothelial growth factor

Background: Vascular endothelial growth factor (VEGF) promotes angiogenesis and vascular permeability. The extent to which VEGF may cause tissue edema in humans has not been established. Objective: To evaluate patients undergoing VEGF gene transfer for evidence of lower-extremity edema. Design: Prospective consecutive case series. Setting: Hospital outpatient clinic. Patients: 62 patients with critical limb ischemia and 28 patients with claudication. Intervention: Gene transfer of VECF DNA. Measurements: Semiquantitative analysis of lower-extremity edema. Results: Lower-extremity edema was observed in 31 of 90 (34%) patients. Edema was less common in patients with claudication than in those with pain at rest (P = 0.016) or ischemic ulcers (P < 0.001), and it was less common in patients with pain at rest than in those with ischemic ulcers (P = 0.017). Treatment was typically limited to a brief course of oral diuretics. Conclusions: Vascular endothelial growth factor may enhance vascular permeability in humans. At the doses of plasmid DNA used in this study, lower-extremity edema responded to oral diuretic therapy and did not seem to be associated with serious sequelae.