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A substance found naturally in the blood vessel lining is thought to contribute towards diseases associated with the circulation system, such as heart failure, high blood pressure, stroke and kidney disease. A study to be published in the open access journal PLoS Medicine looks at the role of asymmetric dimethylarginine (ADMA), which is found in the vessel lining of healthy people but at much higher levels in those with medical conditions associated with damage to the blood vessels.
ADMA is already recognized to be an important indicator of cardiovascular disease: higher levels are found in people with a range of problems of the heart and blood vessel system. These levels have also been used to predict the risk of such problems in otherwise healthy male patients and pregnant women. However, Caroline Smith and colleagues from University College London attempted to uncover whether ADMA actually causes damage rather than just being a marker of risk. They did this by treating cells from the blood vessel lining with high doses of ADMA and measured the effects. The researchers found that a number of genes were more active when the cells were exposed to higher ADMA levels, including those that previous studies suggest are involved in lung, heart and kidney disease. The team also examined tissues from mice with high ADMA levels and found that the genes exhibiting changes were those known to be associated with cardiovascular disease and hypertension.
This exploratory research paves the way for new studies to examine the exact function that those genes responding to higher ADMA levels may play in cardiovascular disease. In the long term, understanding of the mechanisms associated with increased ADMA levels may lead to new strategies for treatment or prevention.
Citation: Smith CL, Anthony S, Hubank M, Leiper JM, Vallance P (2005) Effects of ADMA upon gene expression: An insight into the pathophysiological significance of raised plasma ADMA. PLoS Med 2(10): e264.
CONTACT:
Caroline Smith
University College London
Clinical Pharmacology
5, University Street
London, UK WC1E 6JJ
+44-020-7679-6350
+44-020-7679-6350 (fax)
c.l.smith@ucl.ac.uk
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