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 m itogen that potently stimulates vasodilatation, microvascular hyperpermeabi lity, 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 endothelia l cells (ECs) and vascular smooth muscle cells (VSMCs). Here, we demonstrat e that Ang II enhanced VEGF production in Neuro-2a cells in a dose- and tim e-dependent fashion in the culture media, determined by Enzyme-Linked Immun osorbent Assay (ELISA). The Ang II receptor antagonist Sar1-Ileu8 and hepar in prevented Ang II-induced VEGF release in the culture media. Coincubation of the Neuro-2a cells with Ang II and thrombin increased VEGF release mark edly. However, Ang II-induced VEGF production was inhibited by the transcri ptional inhibitor actinomycin D and protein synthesis inhibitor cycloheximi de. 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 transl ation.