Release date: 2017-12-01
A study led by researchers from the Sanford Burnham Prebys Medical Discovery Institute (SBP) identified a signaling pathway necessary for angiogenesis and the production of new blood vessels from existing blood vessels. The study, published in Nature Communications, may improve existing strategies to improve blood flow in ischemic tissue, such as in atherosclerosis and peripheral vascular disease associated with diabetes.
Dr. Masanobu Komatsu (Source: SBP)
"Our research suggests that the formation of a fully functional vascular requires a protein-activated protein kinase called A-Rs, a mechanism that is essential for the formation of blood vessels and the formation of the lumen." Dr. Masanobu Komatsu, Associate Professor, SBP Nona Lake Campus Say. "This finding is important because it provides new insights into the biological processes that increase blood flow in ischemic tissue."
Prior to this, methods for treating ischemia by manufacturing new blood vessels focused on the delivery of angiogenic growth factors, such as vascular endothelial growth factor (VEGF), to the ischemic area. But all of these studies, including more than 25 Phase II and Phase III clinical studies, have failed to deliver significant benefits to patients.
Komatsu's team combined 3D cell culture with living tissue and found that VEGF promotes angiogenesis, but the resulting vascular structure is chaotic, unstable, and non-functional. "The functional blood vessels need to have a lumen; a pathway that wants a tube-like pathway to allow oxygenated blood and nutrients to pass through the body," Komatsu explains. "The formation of vascular structures is not fully supported by VEGF alone."
"New blood vessels are produced in a similar way to trees; sprouts grow from existing blood vessels and then extend farther and farther like branches to restore the vascular network," said Wangfei Li, a post-doctoral assistant at Komatsu Labs and the first author of the article. . "This study shows that there are obvious steps and signals in controlling this process."
"First, VEGF activates Akt to induce endothelial cell sprouting. Then, R-Ras activates Akt to induce lumen formation," Li explained. "The second step, Akt activated by R-Ras, stabilizes the microtubule skeleton of endothelial cells, creating a stable structure that promotes the formation of lumens."
"We suggest that VEGF and R-Ras are complementary to Akt activation signals, both of which are required for full-function angiogenesis," Komatsu said. "Our next step is to work hard to promote Akt signaling in clinical research."
Our next step is to promote the use of Akt's joint signaling in clinical research; to stimulate R-Ras activation by VEGF through gene therapy or pharmacological methods. " Komatsu said.
Original source:
Fangfei Li, Junko Sawada & Masanobu Komatsu. R-Ras-Akt axis induces infrared lumenogenesis and regulates the patency of regenerating vasculature.Nature Communications 8, Article number: 1720 (2017) doi:10.1038/s41467-017-01865-x
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