Working Groups (thematic description) Action: BM0904 (HDLnet) “HDL- From biological understanding to clinical exploitation” Years: 2010-2014 Participating countries: AT, DK, FI, FR, DE, GR, IT, NL, RS, ES, CH, UK Chair of the Action: Dimitris Kardassis, GR, kardasis@imbb.forth.gr Rapporteur: Prof. Marieta COSTACHE Science Officer: Dr Magdalena RADWANSKA Action Website: https://sites.google.com/site/costbm0904/ Scientific background High-density lipoprotein (HDL) is an attractive target for preventing and curing coronary artery disease (CAD) in view of the inverse association between plasma HDL cholesterol and CAD risk as well as the multiple beneficial, anti-atherogenic properties of HDL. As yet, no effective HDL-tailored therapy of CAD is available. This may be due to the fact that HDLs differ in composition and functionality which necessitates the search for the proper biomarkers to assess and monitor HDL-related CAD risk. Working Groups (thematic description) WG1: HDL Structure Reach agreement on best laboratory practice for the analysis and isolation of HDL particles Identify and quantify proteins and lipids belonging to the different HDL subclasses Describe how HDL composition is altered in humans or animal models with specific mutations in HDL metabolism WG2: HDL function Molecular mechanisms underlying normal HDL functionality and HDL dysfunction in common metabolic stress situations such as dyslipidemia, inflammation, diabetes and acute coronary syndromes WG3: HDL Genetics and regulation Identification of new genes, mutations and polymorphisms affecting HDL levels, structure and function via GWAS in the general population and in patient cohorts; deep re-sequencing of individuals with extreme HDL phenotypes Identification of novel regulatory pathways that affect HDL metabolism WG4: HDL physiology Study HDL physiology in vitro and in vivo and the mechanisms underlying reverse cholesterol transport Elucidate the physiological and pathogenic relevance of novel genes and mutations in known HDL genes on HDL biogenesis, remodelling and structure-function WG5: Epidemiological and clinical validation of biomarkers and therapies Explore and validate the diagnostic efficacy of novel lipid or protein biomarker towards assessment and monitoring of cardiovascular risk in populations and patient cohorts. Assess the impact of natural mutations, polymorphisms or new genes on the variation of HDL-related biomarkers and CAD risk Objectives defined in the MoU The scientific objectives of COST BM0904 (HDLnet) are: a) to increase our understanding of HDL structure, function, physiology and genetics b) to understand HDL dysfunction in pathological conditions such as dyslipidemia, diabetes and acute coronary syndromes; and c) to identify and validate novel HDL-based biomarkers in clinical case-control studies as well population-based cohort studies towards their ability to improve cardiovascular risk prediction and in clinical intervention studies towards their ability to reflect the response to anti-atherogenic therapy. . Scientific deliverables obtained due to networking Lipid and protein composition of different HDL subpopulations and their functions in relation to atheroprotection Role of HDL receptors and transporters in the transcytosis of HDL through the endothelial layer New genetic loci and new variants in known HDL genes that are associated with lipid levels in the population Mechanisms of HDL-mediated cholesterol efflux Regulation of HDL levels by cellular pathways and by drugs Capacity building due to networking Formation of a strong network of European scientists in order to foster collaboration and multidisciplinarity in HDL research Sharing of resources (samples and data of population cohorts, animal models of disturbed HDL metabolism) Dissemination of results (meetings, workshops, publications) Technology transfer (STSMs, training schools) Active involvement of Early Stage Researchers and female scientists Formation of precursor networks for EU fp7 grants COST Visibility Scientific Meetings International Workshops on HDL Publications in scientific journals, Articles in Newsletters, Web site