We need new blood vessels to support neurogenesis and stem cells whenever they are viable. So what will your doctor do with this information to help your recovery? Ignore it is not the answer you want, but will probably get.
Neurons Modulate the Growth of Blood Vessels
A team of researchers at Karlsruhe Institute of Technology (KIT)
shake at the foundations of a dogma of cell biology. By detailed series
of experiments, they proved that blood vessel growth is modulated by
neurons and not, as assumed so far, through a control mechanism of the
vessel cells among each other. The results are groundbreaking for
research into and treatment of vascular diseases, tumors, and
neurodegenerative diseases. The study will be published in the
prestigious journal Nature Communications.
“Our work is pure basic research,“ Professor Ferdinand le Noble of
KIT’s Zoological Institute says, “but provides a completely new
perspective on how blood vessels grow, branch out, or are inhibited in
their growth.” For decades, researchers have been looking for ways to
promote or impede the formation of new blood vessels. Whereas heart
attack and stroke patients would profit from new arteries, cancer
patients would benefit from tumor starving by putting a stop to
ingrowing blood vessels.
The key figures in the newly discovered extremely finely balanced
process are signaling molecules: the brake on growth “soluble FMS-like
tyrosine kinase-1”, referred to as 1sFlt1, and the “vascular endothelial
growth factor”, referred to as VEGF. Even though, so far, it has been
largely unknown how VEGF is regulated by the body, inhibition of this
growth factor has been applied for years already in the treatment of
cancer patients and of certain eye diseases. The therapy, however, is
successful only in part of the patients and has several undesired side
effects.
“So far, research assumed the blood vessels to more or less regulate
their own growth,” explains le Noble. “In case of oxygen deficiency,” he
points out, “tissue, among others, releases the growth factor VEGF,
thus attracting the blood vessels carrying VEGF receptors on their
surfaces. We wanted to know how this blood vessel growth is regulated at
the time of a creature’s birth.” The team around le Noble hence studied
the continuous growth of nerve tracts and circulatory vessels in
zebrafish model organisms. The eggs of zebrafish are transparent and
develop outside of the mother’s body, allowing researchers to watch and
observe the development of organs or even individual cells without
injuring the growing animal.
By means of fluorescent dyes, postgraduate Raphael Wild in a first
step documented colonization of neuronal stem cells and subsequent
vascular budding in the vertebral canal of zebrafish. To understand the
exact process, the team started a detailed biochemical and genetic
analysis.
The researchers proved that at different development stages, the
nerve cells of the spinal cord produce more or less sFlt1 and VEGF and,
in this way, modulate the development of blood vessels. At the early
development stage, neuronal sFlt1 brakes blood vessel growth by binding
and inactivating the growth factor VEGF. In the spinal cord, this
creates an environment poor in oxygen, which is essential to the early
development of the neuronal stem cells. With increasing nerve cell
differentiation, concentration of the soluble sFlt1 decreases
continuously, and the brake on vascular growth is loosened because more
active VEGF is now available. Subsequently, blood vessels grow into the
young spinal cord to provide it with oxygen and nutrients.
In addition, Raphael Wild and his colleague Alina Klems show that the
concentration of the growth factor is crucial as regards the density of
the developing blood vessel network. Whereas, when the “brake” sFlt1 in
nerve cells was switched off completely, a dense network of blood
vessels formed which even grew into the vertebral canal, the growth of
blood vessels was suppressed when sFIt1 was increased. Even small
variations in substance concentration thus led to severe vascular
developmental disorders.
Since vascular cells also have own forms of sFlt1 and VEGF, the
question arose as to whether blood vessel growth may, to a certain
degree, regulate itself. To find out, the researchers applied the still
young and extremely elegant CRISPR/Cas method: Whereas there was no
effect when sFlt1 was switched off only in vascular cells, an intensive
growth of blood vessels was observed when the production of sFlt1 was
switched off in the nerve cells only.
“From the results we conclude that by a fine modulation of sFlt1 and
VEGF, nerve cells very dynamically regulate the density of their blood
vessel network according to requirements or according to the respective
development stage,” le Noble points out. “The previous assumption that
growing blood vessel cells control the succeeding vascular cells is a
cell biology dogma whose foundations are being shaken.”
http://www.kit.edu/kit/english/pi_2017_002_neurons-modulate-the-growth-of-blood-vessels.php
Attached files
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Severely hyperbranched vascular network surrounding the spinal cord (red dotted box) of zebrafish embryo – blood vessels in white (Bild: le Noble/KIT)
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