Vascular networks form and expand by “sprouting,” similar to the way trees grow new branches. The process allows fresh oxygen and nutrients to be delivered to tissues, whether in a developing embryo or a cancerous tumor.
Up until now, scientists thought that the molecular signals to form new sprouts came from outside the vessel. But new research from UNC has shown that signals can also come from within the blood vessel, pushing new blood vessel sprouts outward.
The findings, published in the Sept. 15 issue of the journal Developmental Cell, could give important insights into the formation of the vasculature needed to feed new tumors.
In experiments using mouse embryonic stem cells and mouse retinas, the researchers found that defects in a protein called Flt-1 lead to abnormal sprouts and poor vessel networks. Other research recently showed that levels of Flt-1 protein are particularly low in the dilated and leaky blood vessels that supply tumors with oxygen.
“The blood vessels themselves seem to participate in the process guiding the formation of the vascular network,” said senior study author Victoria L. Bautch, Ph.D., professor of biology at UNC. “They do not just passively sit there getting acted upon by signals coming from the outside in. Rather, they produce internal cues that interact with external cues to grow.”
The growth of new blood vessels can be stimulated by cascades of events within the cell – known as pathways – the most notable of which centers around the three proteins Flt-1, Flk-1 and VEGF. Scientists have known for years that Flk-1 is a positive regulator that responds to VEGF by pulling the emerging sprout outward from its parent blood vessel.
The role of its sister protein Flt-1, however, was not clearly understood. Bautch and colleagues hypothesized that Flt-1 is a negative regulator -- soaking up VEGF molecules so they are not available to interact with Flk-1 and signal for new blood vessels.
The researchers mixed two different types of mouse embryonic stem cells – one batch with normal Flt-1 protein levels, the other with no Flt-1 protein. They found that the genetic makeup of the area at the base of the sprout – rather than at the sprout itself – determined whether the sprout behaved normally or abnormally.
“The cells on each side of sprout produce and send out the soluble form of the protein, blocking the sprout from forming anywhere but in one spot and in one direction,” says Bautch. “So when the sprout first forms, instead of flopping back onto its parent vessel, it has a corridor to push it forward away from the parent.”
Bautch, who is also a member of the Program in Molecular Biology and Biotechnology, the UNC McAllister Heart Institute and UNC Lineberger Comprehensive Cancer Center, notes that the more scientists understand about the sophistication and complexity of the mechanisms guiding the formation of blood vessel sprouts, the better equipped they will be to develop therapeutic interventions to produce or to halt new blood vessels.
Funding for study came from the National Institutes of Health and the American Heart Association. Study co-authors from UNC include John C. Chappell, Ph.D., postdoctoral fellow; and Sarah M. Taylor, graduate student.
Les Lang | Newswise Science News
Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
17.08.2017 | Physics and Astronomy
17.08.2017 | Earth Sciences
17.08.2017 | Physics and Astronomy