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 For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>