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Role of a key enzyme in reducing heart disease identified

Virginia Commonwealth University researchers have identified the role of a key enzyme called CEH in reducing heart disease, paving the way for new target therapies to reduce plaques in the arteries and perhaps in the future, help predict a patient's susceptibility to heart disease.

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1. Key Function Of Nervous System Enzyme Found; Impact On Drug Development Against Alzheimer's
   09-29-2006 · ScienceDaily
   Ever since scientists first elucidated the molecular mechanisms underlying the pathology and loss of nerve cells in Alzheimer's disease, drug companies have been working to develop drugs which will inhibit the outbreak of this severe form of dementia. Now researchers in Munich and Berlin (Germany) have discovered that an enyzme which has a central causal role in Alzheimer's disease happens also to have a key function in the normal development of the nervous system. This enzyme, beta-secretase or BACE1, ensures that nerve fibers (axons) are adequately isolated with sheaths of myelin, enabling rapid conduction of electrical impulses, as well as preventing short-circuits, akin to plastic insulation on electrical wires.
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2. Story ideas from the Journal of Lipid Research
   05-29-2007 · EurekAlert!
   Story ideas from the June 2007 issue of the Journal of Lipid Research include new insight into how low HDL causes heart disease, the role of a key protein in type 2 diabetes, and how fat tissue works.
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3. Enzyme structure reveals new drug targets for cancer and other diseases
   02-14-2008 · EurekAlert!
   Researchers now have a clearer understanding of how a key protein controls gene activity and how mutations in the protein may cause disease. The work could provide new avenues to design drugs aimed at cancer, diabetes, HIV, and heart disease.
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4. UCSD researchers discover variants of natural tumor suppressor
   04-09-2007 · EurekAlert!
   Building on their 2005 discovery of an enzyme that is a natural tumor suppressor, researchers at the University of California, San Diego School of Medicine have now identified two variants of that enzyme which could provide new targets for therapies to treat diabetes, heart and neurological disease.
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5. Key molecular signaling switch involved in allergic disease identified
   10-29-2006 · EurekAlert!
   A research team has identified a key enzyme responsible for triggering a chain of events that results in allergic reaction, according to new study findings published online this week in Nature Immunology.
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6. Advance in understanding of blood pressure gene could lead to new treatments
   02-04-2007 · EurekAlert!
   Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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7. Belly fat may drive inflammatory processes associated with disease
   03-13-2007 · EurekAlert!
   As scientists learn more about the key role of inflammation in diabetes and heart disease, new research from Washington University School of Medicine in St. Louis suggests that fat in the belly may be an important promoter of that inflammation. The researchers have confirmed that fat cells inside the abdomen secrete molecules that increase inflammation. This is the first evidence of a potential mechanistic link between abdominal fat and systemic inflammation.
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8. Lungs' mast cells could provide new treatment target for asthma, other respiratory disease
   01-29-2008 · EurekAlert!
   An enzyme released by mast cells in the lungs appears to play a key role in the tightening of airways that is a hallmark of asthma -- pointing to a potential new target for treatment against the illness.
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9. Mouse with myotonic dystrophy type 1 finds RNA binding proteins at heart of problem
   09-05-2007 · EurekAlert!
   A new mouse model for myotonic dystrophy - the most common form of adult-onset muscular dystrophy - helped Baylor College of Medicine researchers show that levels of CUGBP1, a protein that binds and controls the activity of the genetic material RNA, increase early in affected cells of the animals with the disease. This means CUGBP1 plays a key role in the disorder.
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10. Naturally occurring enzyme can break down key part of Alzheimer's plaques
    10-24-2006 · EurekAlert!
    Scientists have identified a naturally occurring enzyme that can break down a key component of the brain plaques characteristic of Alzheimer's disease. The finding may provide researchers with new opportunities to understand what goes wrong in the brains of Alzheimer's patients and could one day help them seek new therapies.
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