Scientists in Germany may have unlocked the secret behind the human body's ability to develop new blood vessels. The recent discovery could one day lead to better treatment for people suffering from malignant tumors and various diseases.
In a study featured in the journal Nature Communications, Ferdinand Le Noble and his colleagues at the Karlsruhe Institute of Technology (KIT) examined the different processes involved in blood vessel growth. These include how the vessels are formed and branch out, and even how they are inhibited in their growth.
Before this study, it was widely believed that vessel cells made use of a control mechanism to regulate the development of blood vessels.
However, the researchers traced the real control over the process to two signaling molecules: the vascular endothelial growth factor (VEGF) and the soluble FMS-like tyrosine kinase-1 (1sFlt1).
VEGF And 1sFlt1
The VEGF is a protein that helps trigger the formation of new blood vessels, while the 1sFlt1 serves as the one that puts a brake on the process.
Scientists have yet to identify how VEGF production is exactly regulated by the body, but the growth factor has already been used to develop therapies for certain eye diseases and cancer. These treatments, however, have only been partially successful and some even produced undesired side effects on patients.
For their work, Le Noble and his team tested the idea that blood vessels are more or less the ones that modulate their own development.
VEGF is often released by tissues whenever the body experiences oxygen deficiency. This helps attract the blood vessels that carry the necessary VEGF receptors. The research team's goal is to understand how this process of blood vessel formation is modulated during a creature's birth.
To do this, the KIT researchers examined how circulatory vessels and nerve tracts grow continuously in zebrafish models.
Since the animals' eggs are transparent and grow outside of the parent's body, Le Noble and his colleagues were able to witness the development of individual cells and organs without disturbing the growth of the zebrafish.
The researchers then recorded the neuronal stem cell colonization and the vascular budding in the animals' vertebral canal through the help of fluorescent dyes. They also conducted a detailed genetic and biochemical analysis in order to understand the entire process.
The subsequent findings revealed that nerve cells in the animals' spinal cord produced VEGF and sFlt1 at different points in their development, which in turn led to the regulation of blood vessel growth.
During the early stage of development, neuronal sFlt1 inhibits the formation of blood vessels by binding and disabling VEGF. This causes the spinal cord to experience oxygen deficiency, which is necessary for the early formation of neuronal stem cells.
As the body experiences increasing levels of nerve cell differentiation, levels of soluble sFlt1 drop continuously as well. The brake placed on vascular growth is eventually loosened since there are now more active VEGFs available.
Blood vessels also begin to grow into the newly developed spinal cord in order to provide enough nutrients and oxygen.
The researchers also discovered that VEGF concentrations play a key role in determining the density of the growing network of blood vessels.
They found that when the sFlt1is in nerve cells was turned off completely, it led to the formation of a dense blood vessel network that even reached the vertebral canal. However, when the concentration of sFIt1 was increased, it resulted in the suppression of the blood vessel growth.
The research team saw a development of severe vascular problems in organisms that experienced even minor variations in sFIt1 concentrations during their growth.
Le Noble said their study proves that nerve cells are the ones that regulate the formation of blood vessels using a fine modulation of VEGF and sFIt1 concentrations. Their findings serve to challenge the previous assumption that the entire process is controlled by blood vessels themselves.