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Washington: Researchers have identified a signaling pathway that is essential for the growth of new blood vessels from pre-existing blood vessels.
This may be a significant discovery for treatment of narrowing of heart arteries and peripheral vascular disease associated with diabetes. The study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) is important because it may help in revising strategies to improve flow of blood in ischemic tissue.
"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." Masanobu Komatsu, Ph.D., associate professor at SBP's Lake Nona campus said.
There have been efforts to treat ischemia by creating new blood vessels and delivering angiogenic growth factors like vascular endothelial growth factor (VEGF) to ischemic sites. But these efforts have failed to yield results. "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.
"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, both are necessary to generate fully functional blood vessels to repair ischemic tissue," said Komatsu. "Our next step is to work toward promoting the combined signaling of Akt in clinical studies; prompting R-Ras activation through either gene therapy or pharmacologically in parallel with VEGF therapy," said Komatsu.
The findings of this study were published in Nature Communications.