Effects of Angiotensin II on human endothelial cells survival signalling pathways and its angiogenic response

Reduced capillary density (rarefaction) is an early event of cardiovascular disease. The PI-3K–Akt pathway is a key player in anti-endothelial cells (ECs) apoptosis. VEGF is a key growth factor for angiogenesis. We investigated the effect of Angiotensin II (Ang II) on ECs survival signalling and angiogenesis in vitro. We found that Ang II had a biphasic effect on Akt phosphorylation by western blotting analysis. Low concentration Ang II caused a dose-dependent increase in Akt phosphorylation, while high concentration of Ang II led to a decrease of Akt phosphorylation. This effect was negative regulated by its type II receptor. Ang II 10− 4 M induced ECs apoptosis by its type II receptor was completely blocked by VEGF. Cell viability was increased by Ang II 10− 6 M and decreased by Ang II 10− 4 M. It was further decreased by pre-treatment with PI-3K/Akt inhibitor LY294002, but unaffected by p38-MAPK inhibitor SB202190. Ang II 10− 4 M reduced ECs' proliferation and vascular tube length, which were in part regulated by type II receptor. Our findings support a dose-dependent role of Ang II in effect on ECs survival and angiogenesis by PI-3K/Akt pathway. The anti-angiogenic effect of Ang II was mediated by its type II receptor.