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 hypoxia or oxidative stress. However, the functional significance of this VEGF autocrine expression remains undefined. To analyze the role of autocrine VEGF in the endothelial response against injury, cultured bovine aorta endothelial cells (BAEC) were challenged with potentially cytotoxic substances with different chemical structure and pharmacologic properties, namely cytochalasin D (CyD), hydrogen peroxide (H2O2) and cyclosporine A (CsA). Our results revealed that: i. In particular conditions, exposure to potentially cytotoxic agents as CyD, H2O2 or CsA results in significant BAEC cytoprotection rather than injury. ii. The response to the 3 agents is shifted to a cell damaging pattern in the presence of a specific anti VEGF monoclonal antibody (mAb). iii. CyD and H2O2 markedly stimulate the autocrine expression of VEGF mRNA and VEGF protein. In conclusion, the present study reveals a protective 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.
Castilla
M A
MA
Nephrology Department, Fundación Jiménez Díaz, Universidad Autónoma, Instituto Reina Sofía de Investigación Renal, Madrid, Spain.
Caramelo
C
C
Gazapo
R M
RM
Martín
O
O
González-Pacheco
F R
FR
Tejedor
A
A
Bragado
R
R
Arroyo
M V
MV
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D002417:Cattle; D016572:Cyclosporine / Q000633:toxicity; D015638:Cytochalasin D / Q000633:toxicity; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000633:toxicity; D008222:Lymphokines / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D008969:Molecular Sequence Data; D016877:Oxidants / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D007166:Immunosuppressive Agents; D008222:Lymphokines; D016877:Oxidants; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015638:Cytochalasin D; D016572:Cyclosporine; D006861:Hydrogen Peroxide