Gender-specific gene expression in macrophages

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.

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.