Castilla M A, Caramelo C, Gazapo R M, Martín O, González-Pacheco F R, Tejedor A, Bragado R, Arroyo M V
Nephrology Department, Fundación Jiménez Díaz, Universidad Autónoma, Instituto Reina Sofía de Investigación Renal, Madrid, Spain.
Life Sci. 2000;67(9):1003-13. doi: 10.1016/s0024-3205(00)00693-7.
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.
在缺氧或氧化应激条件下，已在内皮细胞中检测到血管内皮生长因子（VEGF）的自分泌表达。然而，这种VEGF自分泌表达的功能意义仍不明确。为了分析自分泌VEGF在血管内皮细胞对损伤反应中的作用，用具有不同化学结构和药理特性的潜在细胞毒性物质，即细胞松弛素D（CyD）、过氧化氢（H2O2）和环孢素A（CsA）刺激培养的牛主动脉内皮细胞（BAEC）。我们的结果显示：i. 在特定条件下，暴露于CyD、H2O2或CsA等潜在细胞毒性剂会导致BAEC显著的细胞保护而非损伤。ii. 在存在特异性抗VEGF单克隆抗体（mAb）的情况下，对这3种试剂的反应转变为细胞损伤模式。iii. CyD和H2O2显著刺激VEGF mRNA和VEGF蛋白的自分泌表达。总之，本研究揭示了血管内皮细胞通过自分泌VEGF产生来抵抗损伤的保护机制。此外，还进一步揭示了伴随这种防御机制VEGF表达显著增加的现象。
