Biomarker discovery sheds new light on heart attack risk of arthritis drugs
2014-12-10
(Press-News.org) A class of drug for treating arthritis - all but shelved over fears about side effects - may be given a new lease of life, following the discovery of a possible way to identify which patients should avoid using it.
The new study, led by Imperial College London and published in the journal Circulation, sheds new light on the 10-year-old question of how COX-2 inhibitors - a type of non-steroidal anti-inflammatory drug (NSAID) - can increase the risk of heart attack in some people.
NSAIDs - which include very familiar drugs such as ibuprofen, diclofenac and aspirin - are widely-used treatments for debilitating inflammatory conditions such as arthritis as well as being used for general pain relief worldwide. NSAIDs are also being investigated for their potential to prevent cancer. COX-2 inhibitors, which include Vioxx and Celebrex, were developed in the 1990s to avoid the risk of stomach ulcers caused by some NSAIDs, but after they were linked to an increased risk of heart attacks, they rapidly fell out of favour and some brands, including Vioxx, were withdrawn.
The new study, in mice and human volunteers, was led by Professor Jane Mitchell and Dr James Leiper. Professor Mitchell, from the National Heart and Lung Institute at Imperial, said: "Although the majority of arthritis sufferers could safely use COX-2 inhibitors, the fear of heart attacks has left some patients confused and worried about their medication and GPs nervous about prescribing them. This problem is made worse because we now know that most NSAIDs, not just COX-2 selective drugs, carry a similar risk of heart attacks in some patients.
"If we could identify which people have an increased risk, these patients could be offered more appropriate treatments - and we can start to look at ways of reducing or averting the risk entirely."
NSAIDs work by preventing the production of prostaglandins - the chemical messengers in tissues and joints that trigger pain and inflammation. Prostaglandins are produced by two different enzymes, known as COX-1 and COX-2, which are found at sites of inflammation as well as in other sites around the body.
The study, funded by the Wellcome Trust, the British Heart Foundation and the Medical Research Council (MRC), looked at where and how removing COX-2 caused changes in gene activity in mice. They found that knocking out COX-2 caused changes in three genes in the kidney which predicted a rise in levels of a molecule linked to cardiovascular disease, called ADMA. In subsequent tests, the researchers found that taking NSAIDs led to a rise in ADMA levels in mice and in 16 human volunteers.
Dr James Leiper, from the MRC Clinical Sciences Centre at Imperial, said: ''ADMA is an independent risk factor for cardiovascular disease. In people increases of ADMA similar to those we found are linked with significant increases in cardiovascular disease and death. Our discovery that COX-2 inhibitors raise ADMA levels provides a plausible mechanism for the increased cardiovascular risk associated with these drugs and provides insights into how this risk might be mitigated'
Professor Mitchell thinks that higher ADMA levels might work as an indicator of which patients are at greater risk of a heart attack.
"If we are right," said Professor Mitchell, "ADMA could be used as a biomarker in a simple blood test to identify who may be at risk, and regular screening would allow GPs to monitor patients' ADMA levels to ensure these remain within safe limits whilst taking the drug." The team are planning a clinical trial to test their idea.
ADMA interferes with the normal function of an amino acid called L-arginine, which plays a key protective role in heart health.
Professor Mitchell said: "In some settings, giving more L-arginine can offset the damaging effects of ADMA, so it's possible that supplements containing L-arginine could provide an antidote to the heart attack risk of NSAIDs. This would be simple to test as L-arginine is already widely available in health food shops as a sports and cardiovascular health supplement. More work is needed for which we would need major funding, but I believe it's worth looking at whether these types of supplements could protect those at risk."
INFORMATION:
For more information please contact:
Sam Wong
Research Media Officer
Imperial College London
Email: sam.wong@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248
Notes to editors
1. Blerina Ahmetaj-Shala, Nicholas S. Kirkby et al. 'Evidence That Links Loss Of Cyclo-oxygenase-1 2 With Increased Asymmetric Dimethylarginine: Novel Explanation of Cardiovascular Side Effects Associated With Anti-inflammatory Drugs.' Circulation, 9 December 2014.
2. NSAIDs, which include ibuprofen and aspirin, are the most commonly used family of drugs in the world. It's estimated that every day, 30 million people worldwide will take an NSAID for relief from pain, fever, and inflammation.
3. About Imperial College London
Imperial College London is one of the world's leading universities. The College's 14,000 students and 7,500 staff are expanding the frontiers of knowledge in science, medicine, engineering and business, and translating their discoveries into benefits for society.
Founded in 1907, Imperial builds on a distinguished past - having pioneered penicillin, holography and fibre optics - to shape the future. Imperial researchers work across disciplines to improve global health, tackle climate change, develop sustainable energy technology and address security challenges. This blend of academic excellence and its real-world application feeds into Imperial's exceptional learning environment, where students participate in research to push the limits of their degrees.
Imperial nurtures a dynamic enterprise culture, where collaborations with industrial, healthcare and international partners are the norm. In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
Imperial has nine London campuses, including Imperial West: a new 25 acre research and innovation centre in White City, west London. At Imperial West, researchers, businesses and higher education partners will co-locate to create value from ideas on a global scale.
http://www.imperial.ac.uk
4. The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Thirty MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. http://www.mrc.ac.uk
ELSE PRESS RELEASES FROM THIS DATE:
2014-12-10
Typhoon Hagupit soaked the Philippines, and a NASA rainfall analysis indicated the storm dropped almost 19 inches in some areas. After Hagupit departed the Philippines as a tropical storm, NASA's Terra satellite passed over and captured a picture of the storm curled up like a cat waiting to pounce when it landfalls in Vietnam on Dec. 11.
The Tropical Rainfall Measuring Mission or TRMM satellite, managed by NASA and the Japan Aerospace Exploration Agency gathered over a week of rainfall data on Hagupit. That rainfall data along with data from other satellites was compiled ...
2014-12-10
COLUMBIA, Mo. - Previous cancer research has revealed that women are less likely than men to suffer from non-sex specific cancers such as cancer of the colon, pancreas and stomach. Scientists theorized that perhaps this trend was due to a protecting effect created by female hormones, such as estrogen, that help prevent tumors from forming. Now, researchers at the University of Missouri have found evidence suggesting that the male hormone testosterone may actually be a contributing factor in the formation of colon cancer tumors.
In his study, James Amos-Landgraf, an assistant ...
2014-12-10
Ants: Ever since agriculture evolved ca 10.000 years ago, plants have been artificially selected to become the fast growing and highly productive varieties we know today. However, humans were not the first to see merit in cultivating their own food, as ants have been doing this for 50 million years. A lineage of South-American ants collect leaves and recycle their own feces to manure a fungus garden for food. New research shows that these ants have an evolutionary history of improvement of their fungal crops.
A joint effort by researchers at the Universities of Copenhagen ...
2014-12-10
ANN ARBOR, Mich. - Urinary tract infections can occur with no apparent cause, and as effectiveness of antibiotics fades, treating them is also becoming less predictable.
University of Michigan Medical School researchers have identified bacterial genes that help the infections spread, providing a potential new target for treating UTIs, a global public health concern mostly affecting women. UTIs lead to lost work time, emergency room visits and health care spending of $3.5 billion in the United States.
The research findings, published in this week's Proceedings of the ...
2014-12-10
A new study by Robert Stahelin, an adjunct associate professor of chemistry and biochemistry at the University of Notre Dame and an associate professor at the Indiana University School of Medicine-South Bend, as well as a member of Notre Dame's Eck Institute for Global Health, investigates how the most abundant protein that composes the Ebola virus, VP 40, mediates replication of a new viral particle.
"In brief, the Ebola virus has just seven proteins that encode in its genome," Stahelin said. "VP40 is critical to the formation of a new viral particle and it does this ...
2014-12-10
Ads can communicate their main message in as little as a tenth of a second, helped by color, according to a new study published in Marketing Science, a publication of the Institute for Operations Research and the Management Sciences (INFORMS).
The Buffer Effect: The Role of Color When Advertising Exposures Are Brief and Blurred is by Michel Wedel, Pepsico Chaired Professor of Marketing at the Robert H. Smith School of Business of the University of Maryland and Rik Pieters, Professor of Marketing at the Tilburg School of Economics and Management of the University of Tilburg ...
2014-12-10
A sex-changing fish called California sheephead (Semicossyphus pulcher) plays a vital role in the food web of kelp forests along the Pacific coast. Commonly found in the waters from Baja California to Point Conception -- although they can sometimes be found as far north as Monterey Bay -- sheephead feed on sea urchins, whose grazing habits can wreak havoc on community composition in kelp forests.
A new study by UC Santa Barbara research biologist Jenn Caselle uses data from three decades of research to document differential exploitation and recovery of sheephead populations ...
2014-12-10
Recent research from the University of Alberta reveals that contrary to current scientific knowledge, there's no atmospheric lead pollution in the province's oil sands region.
William Shotyk, a soil and water scientist who specializes in heavy metal pollution, examined sphagnum moss from 21 separate peat bogs in three locations around the oil sands area, near open pit mines and processing facilities.
After measuring the heavy metal content in the moss samples in his ultra-clean lab at the University of Alberta, Shotyk, based in the Faculty of Agricultural, Life and ...
2014-12-10
A University of Colorado Cancer Center study being presented at the San Antonio Breast Cancer Symposium shows that triple negative breast cancer cells process tryptophan to promote survival while traveling through the body in order to seed new tumor sites.
"I'm not saying that people with metastatic breast cancer shouldn't eat turkey during the holidays, but triple-negative breast cancer appears to have found a way to process tryptophan more quickly, equipping cancer cells to survive while in circulation, which allows them to metastasize," says Thomas Rogers, the paper's ...
2014-12-10
DALLAS - Dec. 10, 2014 - UT Southwestern Medical Center microbiologists have identified key bacteria in the gut whose resources are hijacked to spread harmful foodborne E. coli infections and other intestinal illnesses.
Though many E. coli bacteria are harmless and critical to gut health, some E. coli species are harmful and can be spread through contaminated food and water, causing diarrhea and other intestinal illnesses. Among them is enterohemorrhagic E. coli or EHEC, one of the most common foodborne pathogens linked with outbreaks featured in the news, including ...
LAST 30 PRESS RELEASES:
[Press-News.org] Biomarker discovery sheds new light on heart attack risk of arthritis drugs
