Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Promising target for new atherosclerosis therapies linked to leukemia

03.11.2006
In recent years, scientists studying inflammation and atherosclerosis have seen their respective fields converging. Inflammation is an aspect of the immune response to injury and disease; atherosclerosis, with its characteristic lesions in the blood vessel walls, underlies most cardiovascular disease, including heart attacks and strokes.

Now, in a new study, scientists at The Wistar Institute pursuing a promising new immune-system target for anti-atherosclerosis therapies have discovered another convergence: An unwanted potential side effect of any such therapies is a dangerous blood cancer called chronic myelogenous leukemia, or CML. More positively, the CML seen in the genetic strain of mice used in the study closely mimics human CML, so that the mice offer a new model for studying CML, opening the door for researchers to better understand that disease. The Wistar team's results are featured on the cover of the current issue of the Journal of Experimental Medicine, published October 30.

The Wistar scientists initiated their experiments to build on a series of findings that had suggested that blocking certain enzymes called lipoxygenases could inhibit the kind of chronic inflammation in the blood vessel walls that drives the atherosclerotic process. Even better, blocking these enzymes seemed only to affect one type of immune cell, the macrophage, and to interfere only with its role in chronic inflammation. The acute response of the macrophages to infectious agents like bacteria, critical for protection against disease, remained unfettered.

"We and others had hoped that blocking this enzyme would safely slow or stop certain chronic inflammatory responses that have been linked to atherosclerosis," says Ellen Puré, Ph.D., a professor in the Molecular and Cellular Oncogenesis and Immunology programs at Wistar and senior author on the study. "Now we know that if we go that route, we may also unwittingly be promoting leukemia."

To better understand the details of this inflammatory process as it unfolds in atherosclerosis, the Wistar researchers worked with a strain of experimental mice lacking the gene for a specific pivotal lipoxygenase enzyme. They then crossed these mice with other strains of mice genetically prone to atherosclerosis. Would the resulting mice without the lipoxygenase enzyme be protected from developing atherosclerosis, or would their genetic susceptibility to atherosclerosis win out? Either way, precisely what mechanisms were at work in the vessel walls?

Focused as they were on the atherosclerotic process in the blood vessel walls, the researchers nearly overlooked a significant change taking place in another part of the body: To their surprise, they noticed that the spleens of the mice lacking lipoxygenase became enlarged, dramatically so in some cases. In 15 percent of the mice, the spleens grew 5 to 10 times their normal size at the end of a year.

"As immunologists, we couldn't ignore this," Puré says. "The spleen is an important organ of the immune system."

Exploring their observation, the scientists ascertained that the spleens of all of the mice in the experiments were somewhat enlarged, swollen with cells called granulocytes and macrophages, members of a family of immune cells called myeloid cells. The majority of mice were seen to have myeloid proliferative disease, a precursor to CML. And 15 percent of the mice had full-blown leukemias.

"The enzyme we were looking at is expressed in the progenitor cells in the bone marrow that give rise to all the different types of cells in one branch of the immune system," Puré notes. "So perhaps we shouldn't have been shocked to see that it had an effect on these cells to remove the enzyme from the system."

The silver lining in the situation, Puré says, is that the strain of mice used in their study may be the best model for human CML yet found. The subset of the mice with myeloid proliferative disease closely mimic the asymptomatic early stages of CML, while the 15 percent with clear CML model the crisis, or "blast," stage of the disease.

Franklin Hoke | EurekAlert!
Further information:
http://www.wistar.org

More articles from Health and Medicine:

nachricht Collagen nanofibrils in mammalian tissues get stronger with exercise
14.12.2018 | University of Illinois College of Engineering

nachricht New discoveries predict ability to forecast dementia from single molecule
12.12.2018 | UT Southwestern Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>