Preclinical studies of AdVEGF-DΔNΔC
For the last ten years, in the Finnish research laboratories of A.I.Virtanen Institute, Professor Seppo Ylä-Herttuala's group has evaluated the angiogenic effects of all the members of the vascular endothelial growth factor (VEGF) family in various animal models.
VEGF-DΔNΔC is a proteolytically modified short form of VEGF-D which binds to both VEGF receptor 2 and VEGF receptor 3. VEGF-D is constitutively expressed in many human tissues, including the blood vessel wall. Hypoxia does not regulate VEGF-D expression and proteolytic activation is a key step in forming the maximally active short form of VEGF-DΔNΔC which is relatively soluble in the tissue environment. VEGF-DΔNΔC binds to VEGF receptor 2 and induces signalling through this receptor pathway in a less aggressive but more sustained fashion. Thus, its effects should theoretically be less aggressive as compared to classical VEGF-A, but last longer in tissues. In addition, VEGF-D stimulates stem/progenitor cells in the ischemic tissues which could be a very useful property in ischemic muscles. Thus, VEGF-DΔNΔC seems to be a potentially very useful candidate to induce therapeutic angiogenesis in ischemic tissues.