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.


METHODS
Prospective consecutive case series.


METHODS
Hospital outpatient clinic.


METHODS
62 patients with critical limb ischemia and 28 patients with claudication.


METHODS
Gene transfer of VEGF DNA.


METHODS
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.
Baumgartner
I
I
St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
Rauh
G
G
Pieczek
A
A
Wuensch
D
D
Magner
M
M
Kearney
M
M
Schainfeld
R
R
Isner
J M
JM
D000284:Administration, Oral; D003097:Collateral Circulation / Q000502:physiology; D004247:DNA / Q000008:administration & dosage*; D004232:Diuretics / Q000008:administration & dosage; D004487:Edema / Q000188:drug therapy / Q000209:etiology*; D016228:Endothelial Growth Factors / Q000235:genetics*; D018014:Gene Transfer Techniques / Q000009:adverse effects*; D006801:Humans; D007866:Leg; D008222:Lymphokines / Q000235:genetics*; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000503:physiopathology / Q000628:therapy*; D010957:Plasmids; D011446:Prospective Studies; D020033:Protein Isoforms / Q000235:genetics*; D012008:Recurrence; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004232:Diuretics; D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004247:DNA