Medizinische Universität Graz - Research portal
Selected Publication:
Ebner, B.
Role of Mig12 and Mac30 in the lipidmetabolism of macrophages and foam cells
[ Dissertation ] Medical University of Graz; 2006. pp.
- Authors Med Uni Graz:
- Advisor:
- Desoye Gernot
- Altmetrics:
- Abstract:
- Atherosclerosis is the major human disease which is associated with cholesterol and lipid metabolism. Many cell types are involved in atherogenesis such as macrophages, which are essential components of the host defensive system. As a consequence of an uncontrolled uptake of modified LDL, macrophages differentiate into foam cells. These sells are characterized by an enormous accumulation of cytoplasmic lipid droplets and are a hallmark of all stages of atherosclerotic lesions. The differentiation of macrophages into foam cells is associated with an altered gene expression. The aim of this work was the identification and characterization of so far unknown genes differentially expressed in macrophages and foam cells utilizing a combination of subtractive suppression hybridization and cDNS microarray analysis. A large number of potential target genes could be revealed. Our interest was focused on the characterization of Mig12 and Mac30. Both genes were found to be down-regulated by an excess of cholesterol in vitro as well as in vivo in murine livers. Statin-mediated sterol deprivation resulted in a significant increase of Mig12 and Mac30 gene expression. Co-incubation of statins and mevalonate reversed the statin-induced induction of Mig12. In vitro, liver X receptor (LXR) agonists, which are key regulators of lipid metabolisms enhanced significantly Mig12 gene expression, whereas Mac30 was found to be repressed. In contrast, peritoneal injection of an LXR agonist into mice resulted in the up-regulation of Mig12 and Mac30 in livers in vivo. Fasting and refeeding studies demonstrated that mig12 gene expression is regulated by the nutritional status. In conclusion, two novel targets which are regulated by cellular cholesterol concentrations were identified. We suggest that Mig12 and Mac30 might play important roles in cholesterol metabolism and thus in the development of lipid-associated disorders such as atherosclerosis.