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

Area of Science:

• Cardiovascular Biology
• Endothelial Cell Biology
• Molecular Signaling

Background:

• Reduced capillary density (rarefaction) is an early indicator of cardiovascular disease.
• The PI-3K-Akt pathway is crucial in regulating endothelial cell (EC) apoptosis.
• Vascular Endothelial Growth Factor (VEGF) is vital for promoting angiogenesis.

Purpose of the Study:

• To investigate the effects of Angiotensin II (Ang II) on EC survival signaling and angiogenesis in vitro.
• To elucidate the role of Ang II concentration and its type II receptor in these processes.

Main Methods:

• Western blotting was used to analyze Akt phosphorylation.
• Cell viability assays were performed.
• In vitro angiogenesis assays (e.g., vascular tube length) were conducted.
• Specific inhibitors (PI-3K/Akt inhibitor LY294002, p38-MAPK inhibitor SB202190) were utilized.

Main Results:

• Ang II exhibited a biphasic effect on Akt phosphorylation: low concentrations increased it, while high concentrations decreased it.
• High Ang II (10⁻⁴ M) induced EC apoptosis, an effect mediated by its type II receptor and blocked by VEGF.
• Low Ang II (10⁻⁶ M) increased cell viability, whereas high Ang II decreased it.
• High Ang II reduced EC proliferation and vascular tube formation, partly via its type II receptor.
• The PI-3K/Akt pathway, but not p38-MAPK, was involved in Ang II's effect on cell viability.

Conclusions:

• Ang II plays a dose-dependent role in regulating EC survival and angiogenesis via the PI-3K/Akt pathway.
• The anti-angiogenic effects of high Ang II concentrations are mediated by its type II receptor.