Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb.
BACKGROUND
Preclinical findings suggest that intra-arterial gene transfer of a plasmid which encodes for vascular endothelial growth factor (VEGF) can improve blood supply to the ischaemic limb. We have used the method in a patient.


METHODS
Our patient was the eighth in a dose-ranging series. She was aged 71 with an ischaemic right leg. We administered 2,000 micrograms human plasmid phVEGF165 that was applied to the hydrogel polymer coating of an angioplasty balloon. By inflating the balloon, plasmid DNA was transferred to the distal popliteal artery.


RESULTS
Digital subtraction angiography 4 weeks after gene therapy showed an increase in collateral vessels at the knee, mid-tibial, and ankle levels, which persisted at a 12-week view. Intra-arterial doppler-flow studies showed increased resting and maximum flows (by 82% and 72%, respectively). Three spider angiomas developed on the right foot/ankle about a week after gene transfer; one lesion was excised and revealed proliferative endothelium, the other two regressed. The patient developed oedema in her right leg, which was treated successfully.


CONCLUSIONS
Administration of endothelial cell mitogens promotes angiogenesis in patients with limb ischaemia.
Isner
J M
JM
Department of Medicine, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.
Pieczek
A
A
Schainfeld
R
R
Blair
R
R
Haley
L
L
Asahara
T
T
Rosenfield
K
K
Razvi
S
S
Walsh
K
K
Symes
J F
JF
D000368:Aged; D015901:Angiography, Digital Subtraction; D003097:Collateral Circulation; D016228:Endothelial Growth Factors / Q000008:administration & dosage*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D007866:Leg / Q000098:blood supply*; D008222:Lymphokines / Q000008:administration & dosage*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors