Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inhibiting fatty acids in immune cells decreases atherosclerosis risk

26.07.2010
Scientists at Washington University School of Medicine in St. Louis have found a way to significantly reduce atherosclerosis in mice that does not involve lowering cholesterol levels or eliminating other obesity-related problems.
They report their findings in the July 23 issue of the Journal of Biological Chemistry.

Early areas of atherosclerosis (seen using a red stain that identifies fat) line the artery walls of a mouse fed a high-fat diet (top image), while much less disease is seen in a mouse fed a high-fat diet but unable to make fatty acid synthase in macrophages (bottom image).
Washington University School of Medicine
Atherosclerosis is the process through which fatty substances, such as cholesterol and cellular waste products accumulate in the lining of arteries. Those buildups, called plaques, reduce blood flow through the artery and can contribute to heart attack, stroke and even gangrene. It is common in individuals with obesity-related problems such as high blood pressure, high cholesterol and diabetes.

In this study, the research team inhibited atherosclerosis in mice by interfering with production of a substance called fatty acid synthase. This enzyme converts dietary sugars into fatty acids in the liver, where it plays an important role in energy metabolism. But fatty acids also are involved in atherosclerosis.

“The plaques that clog arteries contain large amounts of fatty acids,” says senior investigator Clay F. Semenkovich, MD. “We engineered mice that are unable to make fatty acid synthase in one of the major cell types that contribute to plaque formation. On a standard Western diet high in fat, the mice had less atherosclerosis than their normal littermates."

Animals can’t survive without fatty acid synthase, so mice in this study were able to make the substance in most of their tissues. They couldn’t manufacture it, however, in macrophages, a type of white blood cell that surrounds and kills invading microorganisms, removes dead cells from the body and stimulates the action of other immune cells. Macrophages are dispatched in response to injury, infection and inflammation.


Semenkovich
Atherosclerosis is the most common cause of heart disease, which is the leading cause of death in the United States. Semenkovich, the Herbert S. Gasser Professor and chief of the Division of Endocrinology, Metabolism and Lipid Research, says doctors tend to concentrate on treating the surrounding risk factors related to atherosclerosis, such as diabetes and high blood pressure, but he says the blockages themselves cause the most serious, life-threatening problems.

“With the current epidemic of obesity and diabetes, people sometimes forget that it’s the blockages in the arteries that really kill people,” he says. “We’ve made progress using statin drugs, for example, that lower cholesterol and fight plaque buildup, but a lot of people who take statins still die from cardiovascular disease. We need better therapies."

These mouse experiments suggest targeting fatty acid synthase in macrophages may provide a potential treatment strategy for humans. The researchers identified factors in the fatty acid pathway that seem to be capable of preventing plaques from blocking arteries in mice. He says those substances – LXR-alpha and ABCA1 – eventually may become drug targets.

“It may be possible, for example, to take macrophages out of humans, inhibit fatty acid synthase in those cells, and then infuse the macrophages back into the same person,” he says. “From what we’ve observed in mice, we would hypothesize that approach might prevent or interfere with plaque buildup in people."

Inhibiting fatty acid synthase in macrophages may not keep blood vessels clean forever, according to Semenkovich, but he says it could lower the risk of heart attacks and strokes while people are making lifestyle changes in order to lose weight, gain control of blood sugar levels or lower triglycerides and cholesterol.

“This discovery allows us to separate atherosclerosis from associated conditions such as diabetes and high cholesterol,” he says. “In fact, in the mice without fatty acid synthase in their macrophage cells, there were no effects on diabetes. Cholesterol in the blood remained the same. But there were fewer blockages in arteries. If a similar approach worked for humans, it could help prevent heart attacks and strokes and give people a chance to get healthier by losing weight and lowering cholesterol."

Schneider JG, Yang Z, Chakravarthy MV, Lodhi IJ, Wei X, Turk J, Semenkovich CF. Macrophage fatty acid synthase deficiency decreases diet-induced atherosclerosis. Journal of Biological Chemistry, July 23, 2010. Online at http://www.jbc.org/cgi/doi/10.1074/jbc.M110.100321

This work was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute of the National Institutes of Health, and by Fellowship Awards from the American Diabetes Association and the American Heart Association.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Jim Dryden | EurekAlert!
Further information:
http://www.wustl.edu

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

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

Climate change: In their old age, trees still accumulate large quantities of carbon

17.08.2017 | Earth Sciences

Modern genetic sequencing tools give clearer picture of how corals are related

17.08.2017 | Life Sciences

Superconductivity research reveals potential new state of matter

17.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>