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Atsushi Otani, Hitoshi Takagi, Hideyasu Oh, Kiyoshi Suzuma, Miyo Matsumura, Eiji Ikeda, Yoshihito Honda; Angiotensin II–Stimulated Vascular Endothelial Growth Factor Expression in Bovine Retinal Pericytes. Invest. Ophthalmol. Vis. Sci. 2000;41(5):1192-1199.
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purpose. Angiotensin II (AII) has been shown to play a role in many vascular
diseases. In the study described, the effect of AII on vascular
endothelial growth factor (VEGF) expression and related intracellular
signaling mechanism was investigated in bovine retinal microcapillary
methods. Cultured bovine retinal microvascular endothelial cells and pericytes
were prepared. VEGF expression was determined by Northern blot analysis
and immunoprecipitation assay. Cell proliferation was assessed by DNA
content 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
time- and dose-dependent manner. Angiotensin II type I receptor
antagonist inhibited this effect. Angiotensin II activates the
transcription of VEGF gene without changing the mRNA half-life, and the
AII responsible region was found in the 5′-flanking region of the VEGF
gene. Angiotensin II also increased the expression of c–fos and
c–jun mRNA, and antisense oligonucleotides against
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 AII might induce angiogenic activity
through a paracrine function of VEGF in retinal microvascular
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