Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS


HDLOMICS Berichtzusammenfassung

Project ID: 37631
Gefördert unter: FP6-LIFESCIHEALTH
Land: Switzerland

Final Report Summary - HDLOMICS (Functional genomics of inborn errors and therapeutic interventions in high density lipoprotein metabolism)

Despite considerable progress in prevention and therapy, coronary artery disease remains the most frequent cause of death. High density lipoproteins (HDL) are promising targets to further reduce morbidity and mortality because low HDL cholesterol plasma concentrations increase cardiovascular risk and because HDL exert many cardio- and vasoprotective functions. There is also great need in improving the diagnostic and prognostic value of the biomarker HDL cholesterol as HDL function is determined by the quality rather than by the quantity of HDL. Therefore, this HDLOMICS project will apply functional genomics approaches including genomics, proteomics and lipidomics as well as new clinical diagnostic tools to study the effects of differential regulation of HDL metabolism on pathophysiological events relevant for atherosclerosis.

50 % of the population of Europe dies of Coronary heart disease (CHD). Of these, current preventive and therapeutic measures, notably lowering of low density lipoprotein (LDL) cholesterol and blood pressure can probably save 30 %. For the remaining 70 %, there will be only hope if new targets for therapeutic intervention are identified. One of the most interesting targets is HDL cholesterol. The great clinical interest in HDL has been generated by numerous epidemiological studies that have found an increased risk of fatal and non-fatal CHD events, such as myocardial infarction, being associated with low HDL cholesterol. In addition, HDL particles as well as HDL-associated proteins and lipids exert a broad scope of anti-atherogenic effects.

In agreement with these protective effects, the development of atherosclerotic lesions could be inhibited or even reverted in animal models by elevation of HDL cholesterol levels. With the exception of nicotinic acid, which increases HDL cholesterol by about 20 % (but with significant side effects), the currently available lipid modifying drugs have little effect on HDL cholesterol levels. Hence, there exists a great interest in finding treatment modalities that increase HDL cholesterol concentration in plasma. Moreover, there is strong evidence that the atheroprotective effect of HDL is determined by the quality rather than by the quantity indicating that there is also great need in improving the diagnostic and prognostic value of the biomarker HDL cholesterol.

The project hopes that the results of the consortium applied with regard to the development of both diagnostics and therapies which ultimately help to reduce morbidity and mortality associated with cardiovascular diseases. In more detail, we expect the development of laboratory tests which can be used for the identification of patients with increased cardiovascular risk and for the monitoring of treatment effects in these patients. In addition, newly identified genes important in HDL metabolism may turn out as important targets for the development of drugs which help to prevent, stop or even cure atherosclerosis. Finally, we expect to develop gene therapy protocols to treat inborn errors of HDL metabolism.

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