Mahmoodzadeh S, Fliegner D, Dworatzek E
Charité-Universitaetsmedizin Berlin, Berlin, Germany.
Handb Exp Pharmacol. 2012(214):23-48. doi: 10.1007/978-3-642-30726-3_2.
Clinical findings show sex differences in the manifestation of a number of cardiovascular diseases (CVD). However, the underlying molecular mechanisms are incompletely understood. Multiple animal models suggest sex differences in the manifestation of CVD, and provide strong experimental evidence that different major pathways are regulated in a sex-specific manner. In most animal studies females display a lower mortality, less severe hypertrophy, and better preserved cardiac function compared with male counterparts. The data support the hypothesis that female sex and/or the sex hormone estrogen (17β-estradiol; E2) may contribute to the sexual dimorphism in the heart and to a better outcome of cardiac diseases in females. To improve our understanding of the sex-based molecular and cellular mechanisms of CVD and to develop new therapeutic strategies, the use of appropriate animal models is essential. This review highlights recent findings from animal models relevant for studying the mechanisms of sexual dimorphisms in the healthy and diseased heart, focusing on physiological hypertrophy (exercise), pathological hypertrophy (volume and pressure overload induced hypertrophy), and heart failure (myocardial infarction). Furthermore, the potential effects of E2 in these models will be discussed.
临床研究结果表明，多种心血管疾病（CVD）的表现存在性别差异。然而，其潜在的分子机制尚未完全明确。多个动物模型显示CVD的表现存在性别差异，并提供了强有力的实验证据，表明不同的主要通路是以性别特异性方式调控的。在大多数动物研究中，与雄性动物相比，雌性动物的死亡率更低、肥大程度较轻，心脏功能保留得更好。这些数据支持这样一种假说，即雌性性别和/或性激素雌激素（17β-雌二醇；E2）可能导致心脏的性别二态性，并使女性心脏病的预后更好。为了更好地理解CVD基于性别的分子和细胞机制并开发新的治疗策略，使用合适的动物模型至关重要。本综述重点介绍了与研究健康和患病心脏中性别二态性机制相关的动物模型的最新研究结果，重点关注生理性肥大（运动）、病理性肥大（容量和压力超负荷诱导的肥大）和心力衰竭（心肌梗死）。此外，还将讨论E2在这些模型中的潜在作用。
