Vascular endothelial growth factor (VEGF) is a highly endothelial cell-specific mitogen capable of stimulating new blood vessel growth (angiogenesis) and collateral- dependent blood flow in vivo. Because of these properties, VEGF has been proposed as a potential pharmacological therapy for the treatment of peripheral arterial disease. Among the five different splice variant isoforms of VEGF, only the shortest (VEGF121) lacks the ability to bind heparin-like molecules. Experiments during Phase I of the project established that VEGF121, like other VEGF isoforms, is active in vivo for the promotion of collateral-dependent blood flow. In addition, consistent with its lack of heparin binding, VEGF121 was found to display pharmacokinetic and clearance characteristics that may confer particular therapeutic advantages to the use of this isoform. During Phase II of the project, VEGF121 will be advanced toward eventual clinical testing of efficacy and of validation for these potential advantages. In particular, a manufacturing process will be developed for the drug. Further experiments will also be undertaken to better define the effects of VEGF121 in an animal model of peripheral arterial insufficiency.
The research is ultimately aimed at developing a therapeutic agent for the treatment of peripheral arterial disease.
| Villanueva, Flordeliza S; Abraham, Judith A; Schreiner, George F et al. (2002) Myocardial contrast echocardiography can be used to assess the microvascular response to vascular endothelial growth factor-121. Circulation 105:759-65 |
