Oxidative stress is nowadays considered as a pivotal factor in inflammatory processes, which are involved in various pathological processes, such as infectious diseases, acute and chronic lung disease and atherosclerosis. However, despite intense research in the last decade, many controversies about oxidative processes are still reported in literature. This is mainly due to the fact that direct detection of free radicals, such as reactive oxygen species (ROS), nitrogen monoxide (NO•) and reactive nitrogen species (RNS), is particularly difficult. Most investigators employ indirect approaches and measure markers of oxidative damage to biomolecules (fingerprint assays). An example is the widely used index for lipid peroxidation in biological samples based on quantification of thiobarbituric acid reactive substances (TBARS), more specifically malondialdehyde (MDA). An analytical approach that permits direct detection of free radicals is electron paramagnetic resonance (EPR).
Each from their own perspective, the four partners are actively involved in research of oxidative stress during inflammatory processes. Until now, they have mainly used indirect techniques to determine oxidative stress. The purpose of this project is first to join efforts to develop novel technology platforms, and second to apply those methods, which are necessary for modern basic research of inflammatory disease processes. Apart from the technical collaboration, the four partners are actively participating to join their strongly complementary expertise in order to tackle the research issue: the role of oxidative stress in inflammatory diseases.
The specific objectives of this project are presented in three work packages (WP) and include:
1. Validation of methods for in vitro quantification of ROS and NO• using EPR as reference method (WP-1);
2. In situ visualisation of selective cell types to track the formation and effects of radicals using modern microscopic imaging techniques (WP-1)
3. Application of these novel techniques to investigate the actual role of ROS in inflammatory processes, with particular focus on macrophage function during intracellular infection with Leishmania, in atherosclerotic plaques and in pulmonary disease (WP-2).
4. Application of these novel techniques to characterise endothelial dysfunction and regenerative capacity of endothelial progenitor cells both in animal models of atherosclerosis and post-infarction ventricular remodelling, and in patients with heart failure (WP-3).
The joint publications in the past prove that the four partners can indeed actively join efforts to resolve research issues. In view of this it is expected that the present project, which is a “real concerted action” (= GOA) by multidisciplinary teams, will achieve a significant part of the objectives proposed in the various work packages.
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