A new study led by researchers identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The finding may improve current strategies to improve blood flow in ischemic tissue, such as that found in atherosclerosis and peripheral vascular disease associated with diabetes.
The research shows that the formation of fully functional blood vessels requires activation of protein kinase Akt by a protein called R-Ras, and this mechanism is necessary for the formation of the hallow structure, or lumen, of a blood vessel.This showed the biological process needed to increase blood flow in ischemic tissues.
Research team used a combination of 3D cell culture and living tissue to show that vascular endothelial growth factor VEGF promotes vascularization, but the vessel structures formed are chaotic, unstable and non-functional. Functional vessels need to have a lumen; a pipe-like opening that allows oxygenated blood and nutrients to travel through the body and VEGF alone cannot fully support the formation of such a vessel structure.
VEGF activates Akt to induce endothelial cells to sprout. Then, R-Ras activates Akt to induce lumen formation. The second step involving Akt activation by R-Ras stabilizes the microtubule cytoskeleton in endothelial cells, creating a steady architecture that promotes lumen formation. VEGF and R-Ras activation of Akt signaling are complementary to each other, both are necessary to generate fully functional blood vessels to repair ischemic tissue.
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