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!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy