Sex differences in the cardiac proteome in myocardial hypertrophy

雄性和雌性哺乳动物基因组的差异只有几个基因位于性别特有的染色体上，这一发现表明，绝大多数性别二型性特征是由于两性存在的基因的差异表达和翻译造成的。尽管大多数差异在大小上不大，但受影响的基因数量很多。今天，应用开发的技术来分析组织蛋白范围，能够系统地评估性别偏向蛋白的表达，并阐明性别二型性在疾病发展和表达中的作用。我们将使用蛋白质组分析来研究男性和女性的心肌肥厚(MH)。我们的假设是，由于高度复杂的蛋白质-蛋白质相互作用网络，性激素启动的蛋白质表达调控在整个蛋白质组中在男性和女性中是不同的。因此，基因和蛋白质的多态在男性和女性中的作用是不同的，并且在蛋白质组性二态的程度上也是如此。这导致男性和女性的MH表型不同，而且个体之间也不同。我们将以小鼠染色体替代品系作为动物模型，研究性别特异性蛋白多态在MH发生发展中的作用。

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.