Sex is a key risk factor for many types of cardiovascular disease. It is imperative to understand the mechanisms underlying sex differences to devise optimal preventive and therapeutic approaches for all individuals. Both biological sex (determined by sex chromosomes and gonadal hormones) and gender (social and cultural behaviors associated with femininity or masculinity) influence differences between men and women in disease susceptibility and pathology. Here, we focus on the application of experimental mouse models that elucidate the influence of 2 components of biological sex—sex chromosome complement (XX or XY) and gonad type (ovaries or testes). These models have revealed that in addition to well-known effects of gonadal hormones, sex chromosome complement influences cardiovascular risk factors, such as plasma cholesterol levels and adiposity, as well as the development of atherosclerosis and pulmonary hypertension. One mechanism by which sex chromosome dosage influences cardiometabolic traits is through sex-biased expression of X chromosome genes that escape X inactivation. These include chromatin-modifying enzymes that regulate gene expression throughout the genome. The identification of factors that determine sex-biased gene expression and cardiometabolic traits will expand our mechanistic understanding of cardiovascular disease processes and provide insight into sex differences that remain throughout the lifespan as gonadal hormone levels alter with age.

中文翻译：

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阐明心血管疾病性别差异背后的机制


性别是多种心血管疾病的关键危险因素。必须了解性别差异背后的机制，以便为所有人设计最佳的预防和治疗方法。生物性别（由性染色体和性腺激素决定）和社会性别（与女性气质或男性气质相关的社会和文化行为）都会影响男性和女性之间在疾病易感性和病理学方面的差异。在这里，我们重点关注实验小鼠模型的应用，该模型阐明了生物性别的两个组成部分——性染色体补体（XX或XY）和性腺类型（卵巢或睾丸）的影响。这些模型表明，除了众所周知的性腺激素影响外，性染色体补体还会影响心血管危险因素，例如血浆胆固醇水平和肥胖，以及动脉粥样硬化和肺动脉高压的发展。性染色体剂量影响心脏代谢特征的一种机制是通过逃避 X 失活的 X 染色体基因的性别偏向表达。其中包括调节整个基因组基因表达的染色质修饰酶。确定决定性别偏见基因表达和心脏代谢特征的因素将扩大我们对心血管疾病过程的机制理解，并深入了解随着性腺激素水平随年龄而变化而在整个生命周期中持续存在的性别差异。