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Eicosanoids and Nitric Oxide: Mediators of Cardiovascular, Cerebral & Neoplastic Diseases

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Characterising novel mediators of disease

European scientists studied the pathways culminating in production of nitric oxide and eicosanoids. Project deliverables have the potential to be used for medical treatments of various cardiovascular and neuronal diseases.

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Eicosanoids are signalling molecules involved in various physiological and pathological processes, including immunity, cardiovascular, cerebral and neoplastic disorders. They are derived from fatty acids through oxygenation by cyclooxygenase and lipoxygenase enzymes. Another molecule involved in various biological processes is nitric oxide (NO). Although it is produced by many cells in the body, secretion via vascular endothelium by endothelial nitric oxide synthases (eNOS) is of particular importance as it regulates blood flow. The aim of the EU ‘Eicosanoids and nitric oxide: Mediators of cardiovascular, cerebral & neoplastic diseases’ (Eicosanox) project was to study the eicosanoid and NO signalling cascades. At the same time it planned to investigate the molecular and biochemical properties of enzymes and molecules implicated in the process, with the goal to develop novel therapeutic strategies and medical treatments. Additionally, project partners performed functional genomic studies to characterise gene expression profiles and regulation of the eicosanoid and NO cascades under normal and disease states. Key enzymes involved in the production process were characterised and their biochemical properties and crystal structure determined. Some of these proteins were proposed as potential drug targets. Scientists uncovered a novel system for production of NO and its physiological effects on the cardiovascular system. An important finding of the project that drew considerable media attention was the revelation that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with cardiovascular risks, altering our perception of NSAID use and side-effects. NSAIDs block the activity of cyclooxygenase enzymes thereby preventing eicosanoid formation. However, scientists were able to identify promising biomarkers in order to predict the relative risk of myocardial infarction associated with different NSAIDs. The Eicosanox project was successful in providing insight into the mechanisms whereby eicosanoids and NO trigger and maintain physiological and pathophysiological processes. The identification of potential drug targets is a promising outcome for the treatment of many affected patients.

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