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Content archived on 2024-06-18

An integrated study on three novel regulatory hubs in megakaryocytes and platelets, discovered as risk genes for myocardial infarction by a genome-wide association and platelet systems biology study

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Research training for heart disease

Young scientists have analysed genetic markers, biomarkers and lifestyle risk factors behind the formation of internal blood clots, a feature seen in cardiovascular disease.

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The EU-funded NETSIM project has successfully supplied and coordinated training activities in the complex molecular picture that lies behind coronary artery disease (CAD). The integrated systems biology and genomics cluster aimed to find out how modifications in DNA sequences can affect the classic CAD phenotype. Genetic studies on tens of thousands of individuals have identified genes mainly related to platelets, the cells responsible for blood clotting. The number of platelets in the blood, their volume and function are risk factors for heart attacks. NETSIM PhD scientists found that the protein encoded by the ARHGEF3 gene regulates the uptake of iron by blood stem cells that produce red blood cells. This exciting discovery prompted the development of a whole raft of novel knock-out zebrafish models to further study these regulators of platelet formation. NETSIM scientists developed new methods to analyse video sequences of clot formation in the zebrafish. This will allow information on a larger number of genes involved in blood clotting. Detailed investigation into genes and proteins responsible for normal platelet volume/number and function indicated the importance of the gene PIK3CG regulated by the EVI1 protein. A similar analysis characterised the function of the RBM8A gene, responsible for reduced platelet numbers. A second cluster investigated the association between tobacco use and CAD in Pakistan. Conclusions from the analysis are that there is no safe level of tobacco use in relation to cardiovascular risk. The role of physical activity was studied in patients with chronic obstructive pulmonary disease or chronic heart failure. NETSIM developed objective measurements for Parkinson’s disease, as well as using physical activity as a quality marker in the rehabilitation unit in hospitals. The results clearly support the use of motion monitoring in chronically ill patients and will further be evaluated. The seamless multidisciplinary approach for the prevention and treatment of CAD promises to deliver major advances in public health and patient care. The young scientists could represent the beginning of a new generation of biomedical specialists with a rounded training from the academic and business world.

Keywords

Genetic, biomarkers, lifestyle, blood clots, training, coronary artery disease, platelet, tobacco, physical activity

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