2006 - Institut für Klinische Chemie - UniversitätsSpital Zürich

Universität Zürich > Medizinische Fakultät > Klinische Chemie, Institut für > Prof. Dr.
Arnold von Eckardstein
Functional genomics of inborn errors and therapeutic interventions in high density
lipoprotein (HDL) metabolism (HDLomics)
Summary / Zusammenfassung
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: 1) Using genome wide
linkage analysis in families with Mendelian inheritance of low HDL cholesterol we will search
new major genes regulating HDL cholesterol. 2) Using high throughput sequencing and allele
specific genotyping technology we will elucidate the impact of mutations in candidate genes for
the variation of HDL cholesterol as well as other lipid traits and the occurrence of cardiovascular
events. 3) Using knock-out and transgenic mouse models we will study the metabolic and vascular
impact of mutated candidate genes on HDL metabolism. 4) We will employ proteomic and
lipidomic tools for the characterisation of HDL and finding specific effects of mutations or
interventions on the structure and function of HDL as well as on lipid metabolism and
atherosclerosis. 5. We will develop and evaluate new therapies including gene therapy protocols
for the correction of inborn errors of HDL metabolism in humans. The ultimate goals of
HDLomics are hence the identification and validation of new targets, which can be used in
differential diagnosis, prognosis, therapy, prevention, and therapy monitoring of low HDL
cholesterol and atherosclerosis. This STREP project is exerted in the course of the 6th framework
programme of the European Commission, involves seven partners from 5 European countries and
is coordinated by the University of Zurich
Weitere Informationen unter http://www.hdlomics.org/
Publications / Publikationen
von Eckardstein A, Hersberger, M, Rohrer, L (2005). Metabolism and biological actions of HDL.
Curr. Opin. Clinical Nutrtion and Metabolic Care. 8: 147-152
von Eckardstein A (2006). Differential Diagnosis of Familial High Density Lipoprotein Deficiency
Syndromes. Atherosclerosis 186: 231-239
Keywords / Suchbegriffe
animal models, atherosclerosis, cardiovascular disease, genetics, inborn errors of metabolism, high
density lipoproteins, lipids, lipidomics, prevention, proteomics, functional genomics, systems
biology
Project Leadership and Contacts / Projektleitung und Kontakte
Prof. Arnold von Eckardstein, MD (Project Leader) arnold.voneckardstein@usz.ch
Project 8608
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