The study appears in the September issue of Molecular Biology of the Cell.
When myosin, a protein that is abundant in muscle and is necessary for muscle contraction, is activated, smooth muscle cells in blood vessel walls contract and raise blood pressure. The cells also proliferate, thickening the walls and narrowing the channel, further increasing blood pressure.
Together, this results in hypertension, according to Dr. Primal de Lanerolle, professor of physiology and biophysics and senior author of the study. The current crop of drugs used to treat hypertension mainly targets contraction of the smooth muscle cells. They do not affect the proliferation of the cells, and the thickening of the walls of blood vessels is presently irreversible.
In the new study, the researchers were able to confirm the increased levels of the activated form of myosin in hypertensive rats, a widely used animal model of hypertension. More importantly, they established why myosin activation is elevated and linked the mechanism to a gene mutation.
The researchers found there was more of a protein called smooth muscle myosin light chain kinase, which activates myosin, in their hypertensive rats than in closely related rats that do not develop hypertension. They also found that there was more of the kinase's messenger RNA, the genetic message the cell uses to make the kinase.
"This told us that whatever was happening to raise levels of the kinase was happening at a genetic level," de Lanerolle said.
Although secondary hypertension may result from another disorder or from some medications, essential hypertension -- the most common form of high blood pressure -- has no known cause. Genetic, environmental and behavioral factors, such as diet, are believed to play a role, but no gene mutations have been identified in proteins that regulate smooth muscle contraction in essential hypertension.
Dr. Yoo-Jeong Han, research associate in physiology and biophysics and lead author of the study, determined the DNA sequence of the stretch of the kinase gene that controls how often it is copied, and thus controls the level of kinase in the cell. She found a mutation in the hypertensive animals -- an insertion of a small extra piece of DNA.
The insertion changes the shape of the gene slightly, Han said, making it easier for a transcription factor (another protein that is essentially an on/off switch for genes) to bind and turn on the kinase gene.
"The result is more copies of the gene, more of the kinase in the cell, and, ultimately, more contraction and proliferation of smooth muscle cells," she said.
The transcription factor that binds the mutated gene more easily is part of a cell signalling pathway. This pathway is activated by a protein called Ras, and mutations in Ras have been previously implicated in numerous human cancers.
"When we blocked Ras signalling in the hypertensive rats, we were able to block the proliferation of the smooth muscle cells in the vessel walls and the development of hypertension," said de Lanerolle.
The next question, according to de Lanerolle, is whether a similar mechanism operates in humans to cause essential hypertension.
"If we find a similar mutation in the equivalent human gene, it will make it easier to identify people at risk for developing hypertension," de Lanerolle said. "People with a genetic predisposition to hypertension would be able to lower their risk through behavioral change or, someday, perhaps, drug therapy."
Jeanne Galatzer-Levy | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction