Angiotensin II-stimulated vascular endothelial growth factor expression inbovine retinal pericytes

PURPOSE. Angiotensin II (AII) has been shown to play a role in many vascula r diseases. In the study described, the effect of AII on vascular endotheli al growth factor (VEGF) expression and related intracellular signaling mech anism was investigated in bovine retinal microcapillary pericytes. METHODS. Cultured bovine retinal microvascular endothelial cells and pericy tes were prepared. VEGF expression was determined by Northern blot analysis and immunoprecipitation assay. Cell proliferation was assessed by DNA cont ent growth assay. Reporter gene studies were performed to identify the AII responsible transcription-activating region of VEGF gene. RESULTS. Angiotensin II induced a significant increase in VEGF mRNA in a ti me- and dose-dependent manner. Angiotensin II type I receptor antagonist in hibited this effect. Angiotensin II activates the transcription of VEGF gen e without changing the mRNA half-life, and the An responsible region was fo und in the 5'-flanking region of the VEGF gene. Angiotensin II also increas ed the expression of c-fos and c-jun mRNA, and antisense oligonucleotides a gainst c-Fos blocked the AII-induced VEGF mRNA expression. The conditioned media of AII-stimulated pericyte cultures had a growth-promoting effect on endothelial cells, and this effect was inhibited almost completely by VEGF neutralizing antibody. CONCLUSIONS. These findings suggest that All might induce angiogenic activi ty through a paracrine function of VEGF in retinal microvascular cells.