(Press-News.org) DALLAS – September 17, 2014 – Researchers at UT Southwestern Medical Center have found that the most common variant of the circulating protein apolipoprotein E, called apoE3, helps repair the lining of blood vessels. Individuals with another variant, called apoE4, do not get the benefit of this repair, putting them at higher risk for cardiovascular disease.
"We believe that we have identified one mechanism by which apoE3 promotes a healthy cardiovascular system and why a genetic variant, apoE4, is detrimental," said Dr. Philip Shaul, Professor of Pediatrics and Vice Chair for Research in the Department of Pediatrics at UT Southwestern.
The team of researchers found that apoE3 binds to a receptor, ApoER2, and that together they act on endothelial cells, which are the guardian cells of blood vessels, to produce a molecule called nitric oxide (NO). Nitric oxide blunts inflammation, a process that contributes to a variety of vascular disorders.
Up to 15 percent of individuals possess the gene coding for apoE4, and why these individuals are at increased risk of atherosclerosis and coronary heart disease had previously been enigmatic. Using both cell culture and mouse models, researchers showed that in contrast to apoE3, apoE4 cannot activate endothelial cells to produce NO. The reparative and anti-inflammatory processes, therefore, do not occur. In fact, apoE4 prevents the actions of apoE3, explaining why even individuals with one copy of the apoE4 gene are at increased risk of vascular disease.
Using mutant proteins, the investigators further determined the structural feature of apoE4 that prevents the protein from having the favorable actions of apoE3 and instead causes it to antagonize cell responses to apoE3.
The findings, recently published online in the Proceedings of the National Academy of Sciences, also suggest a potential preventive treatment for cardiovascular disease in the high-risk individuals who have the apoE4 variant.
"An important mechanism that is lost when people possess apoE4 is the ability to produce NO, which leads to a loss of both the reparative and anti-inflammatory capacities of the endothelium," said Dr. Shaul, who holds the Associates First Capital Corporation Distinguished Chair in Pediatrics. "Now, knowing this information, we believe such individuals may benefit from treatment with an NO donor. There is a form of aspirin, for instance, that is an NO donor," he added.
Whereas there is considerable understanding of the biology of the apoE-ApoER2 tandem in the central nervous system and in Alzheimer's disease, the basis for the cardiovascular impact of the receptor and apoE variants had been perplexing. The new findings on apoE and ApoER2 complement the team's prior work on ApoER2, which revealed an important role for the receptor in the blood-clotting disease known as the antiphospholipid syndrome.
INFORMATION:
Other UT Southwestern researchers on the team include Dr. Joachim Herz, Professor of Molecular Genetics, Neurology and Neurotherapeutics, and Neuroscience, and also holds the Thomas O. and Cinda Hicks Family Distinguished Chair in Alzheimer's Disease Research; Dr. Robert Gerard, Associate Professor of Molecular Biology; Dr. Eunjeong Jung, postdoctoral fellow; Ivan S. Yuhanna, senior research associate; Mohamed Ahmed, research assistant; and Dr. Chieko Mineo, Associate Professor of Pediatrics.
The study was supported by the American Heart Association and the National Institutes of Health. Additional support was provided by the Crystal Charity Ball Center for Research in Pediatric Critical Care and the Associates First Capital Corporation Distinguished Chair in Pediatrics, as well as the Lupe Murchison Foundation, the BrightFocus Foundation, and the Ted Nash Long Life Foundation.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.
Protein variant may boost cardiovascular risk by hindering blood vessel repair
2014-09-17
[Attachments] See images for this press release:
ELSE PRESS RELEASES FROM THIS DATE:
Researchers examine role of hormone in response to ovarian cancer treatment
2014-09-17
The work comes out of the molecular therapeutic laboratory directed by Richard G. Moore, MD, of Women & Infants' Program in Women's Oncology. Entitled "HE4 expression is associated with hormonal elements and mediated by importin-dependent nuclear translocation," the research was recently published in the international science journal Scientific Reports, a Nature publishing group.
The goal of the study was to investigate the role of the hormone HE4 in modulating an ovarian cancer's response to hormones and hormonal therapies. HE4 is a biomarker that is elevated in ovarian ...
Coral growth rate plummets in 30-year comparison
2014-09-17
Washington, DC— A team of researchers working on a Carnegie expedition in Australia's Great Barrier Reef has documented that coral growth rates have plummeted 40% since the mid-1970s. The scientists suggest that ocean acidification may be playing an important role in this perilous slowdown.
In a quest for historical context on the peril facing coral reefs, the team compared current measurements of the growth rate of a section of Australia's Great Barrier Reef with similar measurements taken more than 30 years ago. Their work is published in Geochimica et Cosmochimica ...
Ebola outbreak 'out of all proportion' and severity cannot be predicted
2014-09-17
A mathematical model that replicates Ebola outbreaks can no longer be used to ascertain the eventual scale of the current epidemic, finds research conducted by the University of Warwick.
Dr Thomas House, of the University's Warwick Mathematics Institute, developed a model that incorporated data from past outbreaks that successfully replicated their eventual scale.
The research, titled Epidemiological Dynamics of Ebola Outbreaks and published by eLife, shows that when applying the available data from the ongoing 2014 outbreak to the model that it is, according to Dr ...
EARTH Magazine: The Bay Area's next 'big one' could strike as a series of quakes
2014-09-17
Alexandria, Va. — Most people are familiar with the Great 1906 San Francisco Earthquake and are aware of the earthquake risk posed to the Bay Area — and much of California — by the San Andreas Fault. Most people are not aware, however, that a cluster of large earthquakes struck the San Andreas and quite a few nearby faults in the 17th and 18th centuries. That cluster, according to new research, released about the same amount of energy throughout the Bay Area as the 1906 quake. Thus, it appears that the accumulated stress on the region's faults could be released in a series ...
Rooting out horse-meat fraud in the wake of a recent food scandal
2014-09-17
As the United Kingdom forms a new crime unit designed to fight food fraud — in response to an uproar last year over horse meat being passed off as beef — scientists from Germany are reporting a technique for detecting meat adulteration. They describe their approach, which represents a vast improvement over current methods, in ACS' Journal of Agricultural and Food Chemistry.
Hans-Ulrich Humpf and colleagues note that food fraud is a major global economic problem. But they also say that adding, for example, horse or pork to other meats without disclosure also can cause ...
California's King Fire east of Sacramento
2014-09-17
California's King Fire tripled in size from Monday, September 15 to Tuesday morning, September 16, and current weather conditions are doing nothing more than helping it along. The hot, drought conditions and winds have produced over 12 major fires that still burn all over California. The King Fire is just one of them. It is located east of Sacramento in the Pollock Pines community. Residents have been given mandatory evacuation orders and over 1,600 homes are currently threatened by this fire. It began Saturday September 13 and has spread rapidly through the area fueling ...
Elsevier journal Maturitas publishes position statement on breast cancer screening
2014-09-17
Amsterdam, September 17, 2014 – Elsevier, a world-leading provider of scientific, technical and medical information products and services, today announced the publication of a position statement by the European Menopause and Andropause Society (EMAS) in the journal Maturitas on the topic of breast cancer screening.
Breast cancer is the most prevalent cancer in women, with slightly more than ten percent developing the disease in Western countries. Mammography screening is a well-established method to detect breast cancer. However there are concerns about over diagnosis ...
Toward making lithium-sulfur batteries a commercial reality for a bigger energy punch
2014-09-17
A fevered search for the next great high-energy, rechargeable battery technology is on. Scientists are now reporting they have overcome key obstacles toward making lithium-sulfur (Li-S) batteries, which have the potential to leave today's lithium-ion technology in the dust. Their study appears in the ACS journal Nano Letters.
Xingcheng Xiao, Weidong Zhou, Mei Cai and their colleagues point out that the capabilities of lithium-ion batteries, which power many of our consumer electronics, as well as electric vehicles, have largely plateaued. Scientists have been pursuing ...
Environmentalists and industry duke it out over plastic bags
2014-09-17
Campaigns against disposable plastic shopping bags and their environmental impact recently scored a major win. In August, California lawmakers passed the first statewide ban on the bags, and Governor Jerry Brown is expected to sign it. But the plastic bag industry is not yielding without a fight, according to an article in Chemical & Engineering News, the weekly newsmagazine of the American Chemical Society.
Alexander Tullo, a senior correspondent with C&EN, reports that the anti-bag campaign logged its first small victory in 1990 when Nantucket became the first place ...
Mechanism behind age-dependent diabetes discovered
2014-09-17
Ageing of insulin-secreting cells is coupled to a progressive decline in signal transduction and insulin release, according to a recent study by researchers at Karolinska Institutet in Sweden. The finding, which is published in the journal Diabetes, provides a new molecular mechanism underlying age-related impairment of insulin-producing cells and diabetes.
Ageing is among the largest known risk factors for many diseases, and type 2 diabetes is no exception. People older than 65 years have an increased risk of developing type 2 diabetes if their insulin-producing cells ...