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SFB: Biomembranes: The Role of Endothelial Lipase in Lipid and Lipoprotein Metabolism, Aterogenesis and Vascular Biology
Subproject of: SFB: Biomembranes: Molecular Aspects of Ion Channels
- Abstract
- Generation and Characterization of Conventional and Conditional Knock-Out Mice Lacking Endothelial Lipase
Aims:
To investigate the role of EDL in lipoprotein metabolism and its impact on atherosclerosis development.
To assess the relative impact of macrophage- and endothelium- specific EDL expression (deficiency) on pathogenesis of atherosclerosis.
To determine the impact of macrophage-specific EDL expression on foam cell formation
To elucidate the influence of endothelial EDL on vascular function
Workplan and Methods:
Generation of targeting construct, ES cell experiments, blastocyst injection, complete-ko mice, floxed mice, breeding floxed mice with tissue specific cre-mice, generation of mice lacking EDL exclusively in the liver, endothelial cells and macrophages, creation of recombinant adenovirus expressing cre-recombinase, preparation of anti-mouse-EDL antibody.
Analysis of lipoprotein profile in EDL-ko and tissue specific-ko mice, lipoprotein turnover, lipoprotein tissue distribution, expression of LPL, HL, LDL receptor, SR-BI on mRNA and protein levels.
Athero assays: EDL-ko, endothel-specific-ko and macrophage-specific-ko mice
Foam cell formation: EDL-ko macrophages, cell culture experiments with EDL-ko macrophages including lipoprotein binding, uptake, selective uptake
Vascular physiology with respect to the presence/absence of EDL. Blood vessel reactivity, vasomotion, superoxide anions, Ca2+ concentration in isolated vascular cells, FFA abundance and composition in the blood vessls
- Project Leader:
- Frank Sasa
- Duration:
- 01.10.2001-30.04.2004
- Programme:
- Spezialforschungsbereiche (SFB)
- MUG Research Units
- Division of Molecular Biology and Biochemistry