Regional angiogenesis induced in nonischemic tissue by an adenoviral vector expressing vascular endothelial growth factor
Endothelial Growth Factors
The feasibility of a single administration of a replication-deficient adenovirus (Ad) vector encoding the cDNA for human vascular endothelial growth factor (VEGF) (AdCMV.VEGF) to induce neovascularization in vivo in normal tissue was evaluated in retroperitoneal adipose tissue. Following administration of AdCMV.VEGF (10(9) pfu/50 microliters), maximal VEGF cDNA expression was observed at 2-5 days in the injected adipose tissue. No VEGF protein was detected at > or = 10 days in injected adipose tissue, and there was no increase in serum VEGF levels at any time. In vivo quantification of the number of blood vessels using 30x visualization of the adipose tissue demonstrated an increase in vessel number by 10 days, plateauing by 30 days with a 123% increase in vessel number compared to the control vector AdCMV.Null, despite the fact that no VEGF protein was detected after 5 days. Consistent with the in vivo data, histologic quantification of capillary number demonstrated an increase by day 5, reaching a 38% increase over AdCMV.Null by day 30. These observations demonstrate that an Ad vector carrying the VEGF cDNA is capable of inducing the growth of new blood vessels in a regional fashion in a relatively avascular, normal organ. This suggests in vivo Ad-mediated gene transfer may be useful for therapeutic angiogenesis in the treatment of ischemic cardiovascular disease.