Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

SHR Neuro Cancer Cardio Metab Microb Lipid

Differences in gender-specific gene expression in human and murine macrophages and foam cells

Abstract: Studies on coronary heart disease demonstrate a sex-specific difference in its incidence and severity. The higher prevalence of hypertension, hypercholesterolemia, hyperglycemia, smoking and obesity in men does not suffice to explain the significant gender difference in cardiovascular risk. Thus male gender is one of the 5 dominating risk factors for atherosclerosis and coronary heart disease. The actions of sex hormones on atherogenesis are very complex, with different effects of estrogens or androgens on male or female cells. It is likely that there are many as yet unknown genes involved in the sex-specificity of the atherosclerotic process. To date, surprisingly few studies have addressed gender-related differences in macrophages and foam cells.
This project aims at discovering and functionally characterizing genes that are differentially expressed in male and female macrophages and foam cells. To determine target genes, gene expression profiling of human and murine macrophages and foam cells will be performed. The effects of sex steroid hormones on candidate gene expression levels in those cells will be investigated. Specifically, the following questions will be addressed:
Which genes are differentially expressed in human male and female macrophages and foam cells?
Which genes are differentially expressed in murine male and female macrophages and foam cells?
Are these genes differentially regulated by various sex steroid hormones?
What is the function of these genes?
I expect to identify genes that are expressed in a gender-specific manner. The regulation of up- and downregulated target genes in macrophages and foam cells by various sex steroid hormones will be investigated. Products of candidate genes will be characterized in their biochemical function and their potential role in cholesterol metabolism. The results of the proposed project are expected to contribute to the understanding of gender-specific differences in atherogenesis.

Keywords: biochemistry; molecular biology; biomathematics; atherosclerosis; cholesterol metabolism; foam cells; macrophages; sex steroid hormones; sex-specific gene expression

Project Leader:: Kratky Dagmar

Duration:: 01.09.2006-31.08.2011

Programme:: Einzelprojekt

Type of Research: basic research

Staff: Kratky, Dagmar, Project Leader; Buchebner, Marlene, Co-worker; Rathke, Nora, Co-worker

MUG Research Units: Division of Molecular Biology and Biochemistry

Project partners: Research Institute of Molecular Pathology, Austria
Contact person: Dr. Frank Eisenhaber;; Technische Universität Graz, Institut für Genomik und Bioinformatik , Austria
Contact person: Univ.-Prof. Zlatko Trajanoski;

Funded by: FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria

Project results published: > C16 ceramide is crucial for triacylglycerol-induce... Cell Death Dis. 2012; 3(6):e280-e280; > Adipose triglyceride lipase in immune response, in... Biol Chem. 2012; 393(9):1005-1011; > Pro-angiogenic induction of myeloid cells for ther... Cytotherapy. 2011; 13(4):503-512; > Impaired Rho GTPase activation abrogates cell pola... Cell Mol Life Sci. 2011; 68(23): 3933-3947.; > Farnesoid X receptor represses hepatic human APOA ... J Clin Invest. 2011; 121(9):3724-3734; > Triacylglycerol accumulation activates the mitocho... J Biol Chem. 2011; 286(9): 7418-7428.; > Cholesteryl ester hydrolase activity is abolished ... J Lipid Res. 2010; 51(10): 2896-2908.; > Efficient phagocytosis requires triacylglycerol hy... J Biol Chem. 2010; 285(26):20192-20201; > Synthetic LXR agonist attenuates plaque formation ... J Lipid Res. 2009; 50(2): 312-326.; > Comparison of HSL and KIAA1363: two potential chol... Frontier Lipidology:Lipidomics in Health and Disease; May 10-13, ; Gothenburg, Sweden. 2009.; > Adipose triglyceride lipase deficiency in murine m... Lipidology: Lipidomics in Health and Disease; May 10-13, 2009; Göteborg, Schweden. 2009.