New Study Provides Insights into Regeneration of Blood Vessels
“Our 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.” says Masanobu Komatsu, Ph.D., associate professor at Sanford Burnham Prebys Medical Discovery Institute. “The findings are important because they shed new light on the biological process needed to increase blood flow in ischemic tissues.”
This new research had elucidated a new understanding about the mechanism used by the body to form the lumen of a blood vessel. The study has fueled hope that such a discovery could facilitate new treatments for conditions where the blood supply to a particular body part is restricted.
Angiogenesis is the process by which new blood vessels arise from existing vessels, somewhat akin to how trees grow, with branches stemming out from the trunk. The study found that the process of angiogenesis in the human body requires a particular protein kinase, referred
to as Akt, to be activated by the protein R-Ras.In theory, these observations could help researchers devise methods for regenerating blood vessels and restoring normal blood flow. By establishing how the body develops healthy new blood vessels, researchers could be one step closer to finding ways to induce production as needed.
“Generating new blood vessels is similar to the way trees grow; sprouts develop from existing vessels and then branch out further and further to restore vascularity,” Fangfei Li, Ph.D., postdoctoral associate in Komatsu’s lab said.
Komatsu’s research team used a combination of 3D cell culture and living tissue to show that 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,” explains Komatsu, “and VEGF alone cannot fully support the formation of such a vessel structure.”
“This study shows that there are distinct steps and signals that control the process. First, VEGF activates Akt to induce endothelial cells to sprout. Then, R-Ras activates Akt to induce lumen formation,” Li explained.
“The second step involving Akt activation by R-Ras stabilizes the microtubule cytoskeleton in endothelial cells, creating a steady architecture that promotes lumen formation,” Li added.
“We propose that VEGF and R-Ras activation of Akt signaling are complementary to each other,” said Komatsu. “Both are necessary to generate fully functional blood vessels to repair ischemic tissue.”
The next step is pursuing clinical studies to further investigate the combined signaling of Akt. The idea is to establish a method of prompting R-Ras activation via either gene therapy or via pharmacological means, alongside VEGF treatment.
