A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The findings, published in Nature Communications, may improve current strategies to improve blood flow in ischemic tissue, such as that found in atherosclerosis and peripheral vascular disease associated with diabetes.
“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 SBP’s Lake Nona campus. “The findings are important because they shed new light on the biological process needed to increase blood flow in ischemic tissues.”
Previous efforts to treat ischemia by creating new blood vessels have focused on delivering angiogenic growth factors like vascular endothelial growth factor (VEGF) to ischemic sites. But all of these studies, including more than 25 phase II and III clinical trials, have failed to offer significant benefit to patients.
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.”
“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, says Fangfei Li, Ph.D., postdoctoral associate in Komatsu’s lab and lead author of the paper. “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,” explains Li. “The second step involving Akt activation by R-Ras stabilizes the microtubule cytoskeleton in endothelial cells, creating a steady architecture that promotes lumen formation,” explains Li.
“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,” says 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,” says Komatsu.
The Latest on: New blood vessels
- Doctors keep discovering new ways coronavirus attacks bodyon May 11, 2020 at 5:37 pm
"At the beginning, we didn't know what we were dealing with," said Valentin Fuster, chief physician at Mount Sinai Hospital in New York City, the epicenter of the U.S. outbreak. "We were seeing ...
- New York Reports 521 New Coronavirus Hospitalizations—Bringing State ‘Right Back Where We Started,’ Cuomo Sayson May 11, 2020 at 3:37 pm
New York Gov. Andrew Cuomo said 521 new coronavirus hospitalizations were reported Saturday, bringing the state “right back to where we started on this hellish journey” on March 20—when the state had ...
- 3 Kids Dead After Puzzling New Coronavirus-Linked Inflammatory Illness Hits Young Patientson May 11, 2020 at 1:34 pm
System Inflammatory Syndrome, the new inflammatory illness believed to be related to COVID-19, has infected nearly 100 kids across New York State.
- Men may be more vulnerable to the coronavirus than women. A new study could help explain why.on May 11, 2020 at 12:40 pm
European researchers found concentrations of an enzyme that enables the infection process are higher in men than women among heart failure patients.
- Blood Clots Are Mysteriously Tied to Many Coronavirus Problemson May 11, 2020 at 11:39 am
This is like a storm of blood clots,” says Behnood Bikdeli, a fourth-year cardiology fellow at Columbia University in New York City. Anyone with a severe illness is at risk of developing clots, but ...
- Mysterious illness possibly tied to COVID-19 blamed for deaths of at least 3 children in New Yorkon May 11, 2020 at 10:01 am
Dozens of cases of "pediatric multi-system inflammatory syndrome" are reporting some symptoms similar to Kawasaki Disease and toxic shock syndrome ...
- Three New York Children Have Now Died from Mysterious Illness Linked to Coronaviruson May 11, 2020 at 9:34 am
As of Sunday, the New York State Department of Health is investigating 85 cases of the syndrome, which causes inflammation in blood vessels ...
- Link found between blood vessel inflammation and abnormalities in mitochondrial fissionon May 11, 2020 at 5:18 am
The vast majority of cells in the human body contain tiny power plants known as mitochondria that generate much of the energy cells use for day-to-day activities.
- Temple finds link between blood vessel inflammation, malfunctioning cellular powerhouseson May 11, 2020 at 3:05 am
In new research, scientists at the Lewis Katz School of Medicine at Temple University have uncovered a novel mechanism by which abnormalities in mitochondrial fission in endothelial cells contribute ...
- Blood vessels in obese teens age prematurely, study sayson May 8, 2020 at 12:15 am
Obesity, type 2 diabetes or high blood pressure increase teens' risk of premature blood vessel aging, a new study finds.
via Google News and Bing News