Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutation plays key role in hypertension

15.09.2006
A gene mutation of a key enzyme that regulates smooth muscle contraction and blood pressure in rats has been identified by researchers at the University of Illinois at Chicago. The finding, the first genetic link to muscle contraction and high blood pressure, may lead to improved treatments for hypertension.

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!
Further information:
http://www.uic.edu

Further reports about: Kinase Lanerolle Mutation Myosin contraction hypertension hypertensive

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>