Vascular endothelial growth factor naked DNA gene transfer enhances thrombus recanalization and resolution.
OBJECTIVE
Enhancing thrombus resolution may reduce the long-term complications of venous thrombosis. The aim of this study was to examine whether a sustained release of vascular endothelial growth factor (VEGF) would further improve thrombus recanalization.


METHODS
Inferior caval vein thrombosis was induced in a cohort of 21 male Wistar rats. A plasmid encoding the human VEGF gene (phVEGF) was injected directly into thrombus (30 to 50 microg) and the muscle adjacent to the inferior vena cava (300 to 400 microg). A plasmid containing the gene encoding beta-galactosidase (pCMVbeta) was injected into the same sites of a separate cohort of rats to act as a control. Tissues were harvested after 1 and 2 weeks, and beta-galactosidase activity was measured to estimate transfection efficiency. Muscle and serum VEGF were measured by enzyme-inked immunosorbent assay. Thrombus size, recanalization, and organization were determined by computer-assisted image analysis.


RESULTS
The efficiency of control plasmid transfection into muscle was about 1%. No serum hVEGF was detected in phVEGF- or pCMVbeta-treated animals. Significantly raised levels of hVEGF (P < .01) were detected in the muscle injected with phVEGF after 2 weeks compared with control muscle. There was a significant reduction in thrombus size of 23% (P < .05) and 48% (P < .001) in phVEGF-treated animals compared with pCMVbeta-treated controls after 1 and 2 weeks, respectively. Thrombus recanalization was a significantly greater in the phVEGF-treated group after 2 weeks (mean 19% +/- 2% [SEM]) compared with controls (mean 13% +/- 2%, P < .01). There were no differences in the thrombus organization score.


CONCLUSIONS
VEGF gene therapy of venous thrombus resulted in smaller thrombi with greater recanalization. Angiogenic gene therapy may form the basis of a novel treatment that may improve the resolution of venous thrombi.


CONCLUSIONS
Deep vein thrombosis may lead to residual venous obstruction or reflux and result in post-thrombotic complications that are debilitating and have a substantial socioeconomic impact. Enhancing the resolution of venous thrombi may reduce post thrombotic complications.
Waltham
Matthew
M
Cardiovascular Division, Academic Department of Surgery, GKT, King's College, St Thomas' Campus, London, United Kingdom.
Burnand
Kevin
K
Fenske
Christiane
C
Modarai
Bijan
B
Humphries
Julia
J
Smith
Alberto
A
D000818:Animals; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D015552:Injections, Intralesional; D008297:Male; D010957:Plasmids / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D014682:Vena Cava, Inferior; D020246:Venous Thrombosis / Q000473:pathology / Q000628:therapy*
D019444:Vaccines, DNA; D042461:Vascular Endothelial Growth Factor A