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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New bioimaging technique is fast and economical

21.08.2017 | Medical Engineering

Silk could improve sensitivity, flexibility of wearable body sensors

21.08.2017 | Materials Sciences

On the way to developing a new active ingredient against chronic infections

21.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>