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.
Kou
Baijun
B
Clinical Pharmacology, Clinical Science Research Institute, Warwick Medical School, University of Warwick Coventry, CV2 2DX, UK. koubaijun@yahoo.com
Vatish
Manu
M
Singer
Donald R J
DR
D000804:Angiotensin II / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology