Inside, blood vessels are lined with a single layer of cells. On their surface, these cells bear specific adhesive proteins by means of which they stick close to each other. Normally, this ensures a perfect sealing of the blood vessels.
The most important adhesive protein is the so-called VE-cadherin. It can be destabilized due to different pathological conditions, e.g. due to a sepsis when bacteria have penetrated into the bloodstream and spread within the whole body. This infection causes inflammatory processes which involve leaks in the blood vessel lining. Blood plasma leaks which might result in life-threatening organ swellings as well as tissue bleeding.
To date, there is no means to seal hyperpermeable blood vessels. However, this would be very helpful e.g. for treating patients with pulmonary edema or allergy-induced organ swelling.
Small peptides ensure adhesion
Here, researchers from the "Institut für Anatomie und Zellbiologie" (Institute of Anatomy and Cell Biology) of the University of Würzburg succeeded in taking a first step forward: They have developed small peptide molecules which increase adhesion between vital VE-cadherin adhesive proteins. Thus, the vascular lining is stabilized against inflammatory stimuli.
How do the peptide molecules work? They work just like an adhesive: They bridge the adhesive proteins with each other, because they are designed following the example of the structure by means of which the VE-cadherins stick close to each other. They have a crosslinking effect which they deploy as tandem peptides arranged one after the other - similar to a medical strip with two adhesive ends.
Still far away from application in humans
"These results offer new approaches for the treatment of vascular hyperpermeability", says Prof. Detlev Drenckhahn. However, it is still a long way to go until an application in humans is possible, because the current structure of the molecules is not suitable for such an application.
According to Prof. Drenckhahn it is always difficult to apply peptides to humans, because an unexpected immune response is possible. The next step for the researchers from Würzburg now is to find other molecules resembling the peptides in structure and effect.
Publication in the Journal of Cell Science
The leading researchers from Würzburg Wolfgang-Moritz Heupel, Jens Waschke and Detlev Drenckhahn describe their new approach in the current issue of the Journal of Cell Science. They have worked together with the structural biologist Thomas Müller from the Biocenter who has developed the peptide molecules on the computer. The peptide molecules have been tested in different systems together with the chemist Athina Hübner, the medical scientist Nicolas Schlegel and other employees of the "Institut für Anatomie und Zellbiologie" (Institute of Anatomy and Cell Biology).
The efficiency of the novel molecules could be shown for isolated VE-cadherin adhesive proteins as well as in vivo by means of atomic force microscopy (AFM): If the protective "adhesive" is injected into the blood vessels of mice, their vascular lining does not break down when being exposed to an experimentally generated inflammatory stimulus.
"Endothelial barrier stabilization by a cyclic tandem peptide targeting VE-cadherin transinteraction in vitro and in vivo", Wolfgang-Moritz Heupel, Athina Efthymiadis, Nicolas Schlegel, Thomas Müller, Yvonne Baumer, Werner Baumgartner, Detlev Drenckhahn, Jens Waschke; J Cell Sci. 2009 May 15;122(Pt 10):1616-1625, doi: 10.1242/jcs.040212
Prof. Dr. Detlev Drenckhahn, "Institut für Anatomie und Zellbiologie", University of Würzburg, phone: +49 (0)931 31-2702, firstname.lastname@example.org
Robert Emmerich | idw
Further reports about: > Anatomie > Anatomy > Small peptides > VE-Cadherin > Vessels > Zellbiologie > atomic force microscopy > blood flow > blood plasma > blood vessel > blood vessels of mice > bloodstream > cell death > inflammatory process > inflammatory processes > inflammatory stimulus > peptide molecules > sealing hyperpermeable blood vessels > synthetic biology
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Interdisciplinary Research
20.10.2017 | Materials Sciences
20.10.2017 | Earth Sciences