VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis

Tam, B.Y. et al., Nature medicine, 12:793-800 (2006)

Speaker : 張明俐                                          Time : 2006.10.18 14:10 ~ 15:00

Commentator : 吳梨華 老師                       Place : Room 601

Abstract:

Vascular endothelial growth factor (VEGF) exerts crucial function during pathological angiogenesis and normal physiology. Although VEGF inhibitors hold promise for the treatment of cancer and eye disease, the only monthly prolongation in cancer patient survival and the side effects caused by neutralization of VEGF to the individuals with non-life-threatening illnesses are concerned. Recent studies have revealed that the anti-angiogenesis treatment turns on a feedback response. Besides the resistance generated by the tumor, it remains unknown whether the host also contributes to this feedback response. In this paper, the authors administrated an adenovirus expressing ligand binding soluble extracellular domains of VEGFRs, recombinant VEGF Trap, and VEGFR-2 selective monoclonal antibody, respectively, produced conditional inactivation of VEGF function. By analyzing hematocrit, they observed increased of red blood cell production in both mouse and primate models. This result was associated with near-complete neutralization of VEGF corneal micropocket angiogenesis. Since erythropoietin (Epo) is an important cytokine for erythrocyte production, they found hepatic-Epo was over-secreted in a hypoxia-inducible factor-1α (HIF-1α) independent manner. Alternatively, hepatocyte-produced VEGF could elicit paracrine stimulation of VEGFR2 on neighboring LSECs, followed by reciprocal endothelial repression on hepatocyte Epo production. The authors suggest a model which VEGF-dependent endothelial repression could occur either through lack of a stimulator factor or active production of an inhibitor.

References:

1. Fischer, C. et al. VEGF inhibitors make blood. Nature medicine. 12:732-734, 2006

2. Tam, B.Y. et al. VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis. Nature medicine. 12:793-800, 2006