Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse model reveals potential way to reduce cardiac deaths in kidney patients

31.03.2005


Scientists have identified an important link between kidney damage and cardiac problems, creating new possibilities for treating the primary cause of death in kidney disease patients.



Researchers tracked a chain reaction that leads from kidney damage to weakening of the skeleton to increased phosphorous in the blood. They showed that higher phosphorous levels were directly linked to vascular calcification, a stiffening of the smooth muscle cells that line blood vessels. Vascular calcification leads to enlargement of one of the heart’s four chambers, increased risk of congestive heart failure, heart attack and several other cardiac problems.

Mice treated with an experimental medication that alleviates the skeletal weakening brought on by kidney damage had normal phosphorous levels and decreased signs of vascular calcification.


"We already have treatments available that can control phosphorous levels in the blood, and those should be very helpful for kidney patients," says senior investigator Keith A. Hruska, M.D., the Ira M. Lang Professor of Nephrology and professor of pediatrics and of cell biology and physiology at Washington University School of Medicine in St. Louis. "The drug we used in the mice and other similar agents can treat both the phosphorous levels and skeletal weakening, and those drugs are just entering initial clinical trials."

The study will appear in the April issue of the Journal of the American Society of Nephrology.

Hruska, who is director of nephrology at St. Louis Children’s Hospital, has long been interested in the connections between kidney damage and bone weakening. He and other researchers have uncovered a complex network of links between the skeleton and the kidney. Hormones made in the kidney regulate activity in the skeleton and vice-versa.

Last year, Hruska showed that injections of bone morphogenetic protein-7 (BMP-7) could prevent bone weakening in mice whose kidneys had been damaged or removed.

For the new study, researchers worked with a mouse model of metabolic syndrome, a condition common among patients with chronic kidney disease that includes symptoms such as obesity, high blood pressure and insulin resistance. The condition, which is rapidly increasing in both adults and children, is also associated with higher risks of diabetes and heart disease.

The mice develop metabolic syndrome as a result of both a genetic modification and a high-fat, high-cholesterol diet. To simulate chronic kidney disease, scientists damaged or removed part of the kidney. This led to a shutdown of cells that regularly dismantle and rebuild bones, causing vascular calcification.

The body normally takes minerals like calcium and phosphorous circulating in the bloodstream and deposits them in the bones during bone reconstruction. With those processes shut down, scientists theorized, the bloodstream levels of minerals increase, raising pressure to deposit them elsewhere.

Hruska and his colleagues first showed that injection of BMP-7, previously shown to stop the bone disorder, also stopped vascular calcification. In another group of experimental mice, injections of a substance that binds to compounds with phosphorous but has no effect on the skeleton also stopped vascular calcification, proving that phosphorous was the key link.

"Serum phosphorous is a direct stimulus to the smooth muscle cells that line blood vessels, causing them to take on characteristics very similar to osteoblasts, the cells that form bone," Hruska explains.

The changed smooth muscle cells can deposit minerals outside their membranes, dramatically decreasing the flexibility of blood vessels and increasing the work the heart has to do to create a pulse.

"Vascular stiffness happens to patients with end-stage kidney failure when they go on dialysis, and it leads to many dangerous cardiovascular complications," Hruska says. "This study shows us that by treating the skeleton or otherwise decreasing phosphorous levels, we have the potential to produce a decrease in vascular calcification and marked improvements in cardiovascular outcome."

To follow up, Hruska plans a more direct study of the effects of BMP-7 on vascular calcification and further investigation of the skeleton-kidney links that lead to bone weakening in patients with kidney damage.

Michael C. Purdy | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>