Sex differences in the cardiac proteome in myocardial hypertrophy

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The finding that male and female mammalian genomes differ by only a few genes located on sex-specific chromosomes implies that the vast majority of sexually dimorphic traits result from the differential expression and translation of genes that are present in both sexes. Although most differences are modest in size, the number of affected genes is substantial. Today the application of techniques developed to analyze the proteins of a tissue proteomewide enables the systematic evaluation of sex biased protein expression and the elucidation of the role of the sex-dimorphism in the development and expression of a disease. We will use proteome analysis to investigate myocardial hypertrophy (MH) in males and females. Our hypothesis is that due to highly complex networks of protein-protein interaction regulation of protein expression initiated by sex-hormones differs in males and females proteome-wide. As a consequence, polymorphisms in genes and proteins act in males and females differently and extent in this way sex-dimorphisms in the proteome. This leads to different phenotypes of MH between males and females, and, moreover between individuals. We will use chromosome substitution strains of the mouse as an animal model for studying the influence of sex-specific protein polymorphisms in the development of MH.