Increased production of vascular endothelial growth factor (VEGF) by angiotensin II in neuro-2A cells

Vascular endothelial growth factor (VEGF) is an endothelial cell specific mitogen that potently stimulates vasodilatation, microvascular hyperpermeability, and angiogenesis. VEGF is synthesized and secreted in different cell types by various agents, including vasoconstrictor angiotensin II (Ang II). Knowledge about Ang II-induced VEGF release is still limited to endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Here, we demonstrate that Ang II enhanced VEGF production in Neuro-2a cells in a dose- and time-dependent fashion in the culture media, determined by Enzyme-Linked Immunosorbent Assay (ELISA). The Ang II receptor antagonist Sar1-Ileu8 and heparin prevented Ang II-induced VEGF release in the culture media. Coincubation of the Neuro-2a cells with Ang II and thrombin increased VEGF release markedly. However, Ang II-induced VEGF production was inhibited by the transcriptional inhibitor actinomycin D and protein synthesis inhibitor cycloheximide. Furthermore, Ang II significantly enhanced thrombin receptor expression. These results suggest that Ang II receptor activation may be involved in the production of VEGF, which is dependent on both transcription and translation.