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!
Are there sustainable solutions in dealing with dwindling phosphorus resources?
16.10.2017 | Leibniz-Institut für Nutzierbiologie (FBN)
Strange undertakings: ant queens bury dead to prevent disease
13.10.2017 | Institute of Science and Technology Austria
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...
It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...
Mercury, our smallest planetary neighbor, has very little to call an atmosphere, but it does have a strange weather pattern: morning micro-meteor showers.
Recent modeling along with previously published results from NASA's MESSENGER spacecraft -- short for Mercury Surface, Space Environment, Geochemistry and...
10.10.2017 | Event News
10.10.2017 | Event News
28.09.2017 | Event News
16.10.2017 | Physics and Astronomy
16.10.2017 | Earth Sciences
16.10.2017 | Physics and Astronomy