The researchers injected into rabbits with a version of PAOD a gene-carrying molecule, called a plasmid, which carried a gene that is the blueprint for a protein known as the "zinc-finger-activating" (ZFP) transcription factor. Transcription factors are proteins that switch on other genes.
In the rabbits, the gene produced ZFP transcription factor that successfully activated a key blood-vessel-growth gene, called VEGF, whose protein product triggers blood vessel growth, found the researchers.
Importantly, the researchers demonstrated that this plasmid stimulated the production of three different forms of VEGF, much as the body would on its own. The researchers said they believe that the latest finding is an important advance in the field of therapeutic angiogenesis -- the process of blood vessel growth -- because past studies of VEGF in humans have only involved one form of VEGF and have seen only limited success..
In addition to stimulating new vessel growth and improving perfusion in the damaged leg tissue, the treatment also appeared to prevent the programmed cell death, known as apoptosis, of muscle cells starved of blood supply but not yet dead, the researchers reported.
The results of the Duke study, led by cardiologist Brian Annex, M.D., are scheduled to be published in the Oct. 19, 2004, issue of the journal Circulation, and are available on-line at http://circ.ahajournals.org/.
"Peripheral arterial obstructive disease, which has a national incidence approaching that of coronary artery disease
Contact: Richard Merritt
Duke University Medical Center