Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find protein mechanism for potential atherosclerosis development

11.04.2003


Inactivating a protein that helps regulate the proliferation of vascular cells increases the chance of developing atherosclerosis, a major cause of heart disease, researchers at UT Southwestern Medical Center at Dallas have discovered.



Vascular vessels endure constant pounding and considerable stresses associated with blood flow. Vascular smooth muscle cells play an important role in the development of blood vessels, providing structural integrity and the ability to dilate and constrict. The low-density lipoprotein receptor-related protein (LRP1) helps regulate the proliferation and movement of these smooth muscle cells, presumably because LRP1 forms a complex with the receptor for platelet-derived growth factor (PDGF).

In findings reported in today’s issue of Science, a UT Southwestern research team led by Dr. Joachim Herz, professor of molecular genetics and in the Center for Basic Neuroscience, discovered that inactivating LRP1 in vascular smooth muscle cells caused the overexpression of PDGF receptor and abnormal PDGF receptor signaling in mice. Smooth muscle cells proliferated and the vessel wall became highly susceptible to cholesterol buildup.


“We used gene targeting to unravel a mechanism that controls and holds smooth muscle cell proliferation and migration in check,” said Dr. Philippe Boucher, postdoctoral researcher in molecular genetics and first author of the study. “This process is hyperactive in atherosclerosis.”

The absence of LRP1 is unlikely to occur in humans, Herz said, but the research emphasizes the importance of PDGF signaling in the development of atherosclerosis.

Atherosclerosis is a buildup of cholesterol and fatty substances in the lining of arteries. Smooth muscle cells respond to this buildup by proliferating and taking up more cholesterol, resulting in plaque formation. Continued expansion of this plaque leads to arterial obstruction, which often results in heart attack or stroke.

“We wanted to find out whether the smooth muscle cells would abnormally proliferate after LRP1 was inactivated. They do, and the vessel wall is very susceptible to high cholesterol,” said Herz.

The researchers also discovered that Gleevec – a drug used successfully to treat chronic myeloid leukemia – significantly reduced the development of the vessel abnormalities that lead to atherosclerosis. In cancer cells, Gleevec blocks certain signals and prevents a series of chemical reactions that cause cells to rapidly grow and divide.

“We effectively found that Gleevec could reduce atherosclerosis in our mouse models by about 50 percent,” Herz said.

Herz cautioned that the use of Gleevec in this research does not imply it is an alternative therapy for people with high cholesterol.

“It’s better to keep cholesterol levels down and prevent these pathways from being activated,” he said. “The key to preventing atherosclerosis has not changed. People need to keep their blood pressure down, control cholesterol and control diabetes.”


Other UT Southwestern researchers involved in the study were Dr. Wei-Ping Li, assistant professor of cell biology; Dr. Richard Anderson, chairman of cell biology; and Dr. Michael Gotthardt, former postdoctoral researcher at UT Southwestern and now an assistant professor at the Max-Delbrück Center in Berlin.

The research was supported by the National Institutes of Health, the Alzheimer’s Association and the Perot Family Foundation.

Susan Morrison | EurekAlert!
Further information:
http://www.swmed.edu/

More articles from Life Sciences:

nachricht The Secret of the Rock Drawings
24.05.2019 | Max-Planck-Institut für Chemie

nachricht Chemical juggling with three particles
24.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New studies increase confidence in NASA's measure of Earth's temperature

A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.

The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...

Im Focus: The geometry of an electron determined for the first time

Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.

The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...

Im Focus: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

On Mars, sands shift to a different drum

24.05.2019 | Physics and Astronomy

Piedmont Atlanta first in Georgia to offer new minimally invasive treatment for emphysema

24.05.2019 | Medical Engineering

Chemical juggling with three particles

24.05.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>