Expression of VEGF xxx b‐the inhibitory isoforms of VEGF, in human and rat tissues

Abstract

Vascular endothelial growth factor (VEGF), a potent angiogenic factor, is upregulated in all known tumours and other instances of angiogenesis, but also expressed in most normal tissues. We recently showed that use of alternate, distal, splicing acceptor site in exon 8 results in a family of alternative isoforms, VEGFxxxb that are not upregulated in cancer and are inhibitory to isoforms formed from proximal splicing in exon 8. With Western blotting and enzyme-linked immunoassay, VEGFxxxb was detected in most human and rat tissues by using anti-VEGFxxxb specific antibodies. VEGFxxxb accounts for 21.5% to 85.1% of total VEGF in different rat tissues (including central nervous system, gastrointestinal tract, cardiovascular tissues, testes, muscle, spleen and lung). In kidney, the organ VEGF165b was originally cloned from, 35.1% of total VEGF was VEGFxxxb. In summary, VEGFxxxb is an endogenously expressed protein detected in most human and rat tissues. As a relatively high percentage of endogenous VEGF is VEGFxxxb, and these isoforms are inhibitory to conventional VEGF isoforms, regulation of expression may be a key determinant of physiological and pathological angiogenesis. This work was funded by Wellcome Trust, UK