1998 Russell et al in matrix culture without growth factor in human umbilical vein endothelial cells (HUVEC), the addition of recombinant NRG 3 (a ErbB3 ErbB4 ligand) culture 10d, found that NRG 3 (100ng ml) allows the number of HU VEC an increase of 25 times with 10ng ml the effect of vascular endothelial growth factor (VEGF). Applications can significantly inhibit VEGF-stimulated cells increase in the number of anti-VEGF antibody, but not affect NRG 3 due to the number of HUVEC increased, indicating that NRG 3 HUVEC proliferation effect has nothing to do with VEGF. HUVEC, its application of the two-dimensional collagen gel matrix culture by adding 24 ~ 36h after NRG 3 lumen-like structures formed lengthwise in HUVEC, will not affect the anti-VEGF antibody NRG this angiogenic effect. Corneal angiogenesis model in rats applications containing different doses of NRG or VEGF sustained-release tablets implanted eyes of 7d found, 10ngNRG can induce new blood vessel formation, 50ng can significantly promote new blood vessel formation; role of VEGF similar but does not rely on VEGF. Bagheri is found that The HRG stimulate of breast cancer the epithelial cells VEGFmRNA and protein expression, adding HRG1 to 9hVEGFmRNA increased 2-6 times, can stimulate endothelial cells to produce luminal-like structure, the application of anti-HER2 monoclonal antibody or anti-VEGF monoclonal antibodies this effect can be blocked, this angiogenesis is VEGF dependent. Yen also observed in other tumor cells to a similar result.