Role of vascular endothelial growth factor (VEGF) in endothelial cell protection against cytotoxic agents

Autocrine expression of VEGF has been detected in endothelial cells under h ipoxia or oxidative stress. However, the functional significance of this VE GF autocrine expression remains undefined. To analyze the role of autocrine VEGF in the endothelial response against injury, cultured bovine aorta end othelial cells (BAEC) were challenged with potentially cytotoxic substances with different chemical structure and pharmacologic properties, namely cyt ochalasin D (CyD), hydrogen peroxide (H2O2) and cyclosporine A (CsA) Our re sults revealed that: i. In particular conditions, exposure to potentially c ytotoxic agents as CyD, H2O2 or CsA results in significant BAEC cytoprotect ion rather than injury. ii. The response to the 3 agents is shifted to a ce ll damaging pattern in the presence of a specific anti VEGF monoclonal anti body (mAb). iii. CyD and H2O2 markedly stimulate the autocrine expression o f VEGF mRNA and VEGF protein, In conclusion, the present study reveals a pr otective mechanism of endothelial cells against injury involving autocrine VEGF production. Moreover, the occurrence of a significant increase in VEGF expression accompanying this defensive mechanism is further disclosed. (C) 2000 Elsevier Science Inc. All rights reserved.