Effects of angiotensin II on human endothelial cells survival signalling pathways and its angiogenic response.
Kou B., Vatish M., Singer DRJ.
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.