Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Age-Related Stem Cell Loss Prevents Artery Repair And Leads To Atherosclerosis

15.07.2003


Aging has long been recognized as the worst risk factor for chronic ailments like atherosclerosis, which clogs arteries and leads to heart attacks and stroke. Yet, the mechanism by which aging promotes the clogging of arteries has remained an enigma.



Scientists at Duke University Medical Center have discovered that a major problem with aging is an unexpected failure of the bone marrow to produce progenitor cells that are needed to repair and rejuvenate arteries exposed to such environmental risks as smoking or caloric abuse.

The researchers demonstrated that an age-related loss of particular stem cells that continually repair blood vessel damage is critical to determining the onset and progression of atherosclerosis, which causes arteries to clog and become less elastic. When atherosclerosis affects arteries supplying the heart with oxygen and nutrients, it causes coronary artery disease and puts patients at a much higher risk for a heart attack.


The researchers’ novel view of atherosclerosis, based on experiments in mice, constitutes a potential new avenue in the treatment of one of the leading causes of death and illness in the U.S., they said. Just as importantly, they continued, this loss of rejuvenating cells could be implicated in a broad range of age-related disorders, ranging from rheumatoid arthritis to chronic liver disease.

The results of the Duke research were posted early (July 14, 2003) on the website of the journal Circulation, (http://circ.ahajournals.org). The study will appear in the July 29, 2003, issue of the journal.

At issue is the role of stem cells, which are immature cells produced in the bone marrow that have the potential to mature into a variety of different cells. The Duke team examined specific stem cells known as "bone-marrow-derived vascular progenitor cells" (VPCs).

The researchers believe that it might ultimately be possible to forestall or even prevent the development of atherosclerosis by injecting these cells into patients, or to induce the patient’s own stem cells to differentiate into progenitor cells capable of arterial repair.

"Our studies indicate that the inability of bone marrow to produce progenitor cells which repair and rejuvenate the lining of the arteries drives the process of atherosclerosis and the formation of plaques in the arteries," said Duke cardiologist Pascal Goldschmidt, M.D., chairman of the Department of Medicine. "For a long time we’ve known that aging is an important risk factor for coronary artery disease, and we’ve also known that this disease can be triggered by smoking, bad diet, diabetes, high blood pressure and other factors.

"But if you compare someone who is over 60 with someone who is 20 with the same risk factors, there is obviously something else going on as well," he continued. "The possibility that stem cells may be involved is a completely new piece of the puzzle that had not been anticipated or appreciated before. These findings could be the clue to help us explain why atherosclerosis complications like heart attacks and strokes are almost exclusively diseases of older people."

Doris Taylor, Ph.D. a senior member of the research team, sees these findings leading researchers into new areas of investigation.

"For the first time we are beginning to an insight into how aging and heart disease fit together -- we’ve know they go hand-in-hand – but we haven’t understood why," she said. "Understanding that we either run out of progenitor cells or that they don’t work as well is a big molecular clue to what might be going on in the whole aging process.

"We are excited that as we unravel the mechanisms of this process, we will be able to look deeper into heart and vascular disease, as well as other disease," she added. "These studies form the basis of future collaborations."

In their experiments, the Duke team used mice specially bred to develop severe atherosclerosis and high cholesterol levels. The researchers injected bone marrow cells from normal mice into these atherosclerosis-prone mice numerous times over a 14-week period. As a control, an equal of number of the same kind of atherosclerosis-prone mice went untreated.

After 14 weeks, the mice treated with the bone marrow cells had significantly fewer lesions in the aorta, despite no differences in cholesterol levels. Specifically, the researchers detected a 40-60 percent decrease in the number of lesions in the aorta, the main artery carrying blood from the heart.

Using specific staining techniques on the aortas, the researchers were able to determine that the donor bone marrow cells "homed in" on areas where atherosclerotic lesions are most common, especially where smaller vessel branches take off from larger vessels. These areas tend to experience "turbulence" of blood.

When the researchers examined the vessels under a microscope, it appeared that the bone marrow cells not only migrated to where they were needed most, but that they differentiated into the proper cell types. Some turned into endothelial cells lining the arteries, while others turned into the smooth muscle cells beneath the endothelium that help strengthen the arteries.

To further prove that the donor bone marrow cells were responsible for rejuvenating arteries, the scientists measured in the endothelial cells the lengths of structures known as telomeres at the end of chromosomes. They found that the telomeres in the endothelial cells were longer in the treated mice than the untreated mice. Over time, telomeres are known to shorten as the organism ages.

The researchers also injected these atherosclerotic mice with donor cells from older mice as well as from younger, pre-atherosclerotic mice.

"We found that the bone marrow cells from the young mice had a nearly intact ability to prevent atherosclerosis, while the cells from the older mice did not," Goldschmidt explained. "This finding suggests that with aging, cells capable of preventing atherosclerosis that are normally present in the bone marrow became deficient in the older mice that had developed atherosclerosis."

Once the repair cells from the marrow become deficient, inflammation develops and leads to increase in inflammation markers (such as CRP). By providing competent bone marrow cells, the investigators were able to suppress the inflammation and its blood markers.

While the direct use of stem cells as a treatment may be many years off, the researchers said it is likely that strategies currently used to reduce the risks for heart disease – such as lifestyle modifications and/or different medications – preserve the collection of these rejuvenating stem cells for a longer period of time, which delays the onset of atherosclerosis.

For Goldschmidt, a major question is whether researchers can somehow use these cells to restore the integrity of the circulatory system of patients who already have a lifetime of atheroslerosis.

"We need to look at the possibility of re-training stem cells that would otherwise be targeted to a different organ system to help repair the cardiovascular system," he said. "Another interesting question is whether rheumatoid arthritis, as an example of chronic inflammatory disorders, causes stem cell loss, since such arthritis is a risk factor for coronary artery disease. The chronic process of joint disease could consume stem cells that could otherwise be used for the repair of the cardiovascular system. We are just beginning to appreciate the links between stem cells and cardiovascular disease."

The research was supported by the National Heart Lung Blood Institute and the Stanley Sarnoff Endowment for Cardiovascular Science.

Other members of the Duke team include: Frederick Rauscher, M.D., Bryce Davis, Tao Wang, M.D., Ph.D., Priya Ramaswami, Anne Pippen, David Gregg, M.D., Brian Annex, M.D., and Chunming Dong, M.D.

Contact sources

Pascal Goldschmidt , (919) 668-1755
Golds017@mc.duke.edu
Doris Taylor , (919) 684-4484
Dataylor@duke.edu

Richard Merritt | dukemed news
Further information:
http://dukemednews.org/news/article.php?id=6765

More articles from Health and Medicine:

nachricht New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University

nachricht Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine

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: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Desert ants cannot be fooled

23.11.2017 | Life Sciences

By saving cost and energy, the lighting revolution may increase light pollution

23.11.2017 | Earth Sciences

Retreating permafrost coasts threaten the fragile Arctic environment

23.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>