Blenck Christa L, Harvey Pamela A, Reckelhoff Jane F, Leinwand Leslie A
From the Department of Molecular, Cellular, and Developmental Biology & BioFrontiers Institute, University of Colorado, Boulder (C.L.B., P.A.H., L.A.L.); and Women's Health Research Center and Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.F.R.).
Circ Res. 2016 Apr 15;118(8):1294-312. doi: 10.1161/CIRCRESAHA.116.307509.
Nearly one-third of deaths in the United States are caused by cardiovascular disease (CVD) each year. In the past, CVD was thought to mainly affect men, leading to the exclusion of women and female animals from clinical studies and preclinical research. In light of sexual dimorphisms in CVD, a need exists to examine baseline cardiac differences in humans and the animals used to model CVD. In humans, sex differences are apparent at every level of cardiovascular physiology from action potential duration and mitochondrial energetics to cardiac myocyte and whole-heart contractile function. Biological sex is an important modifier of the development of CVD with younger women generally being protected, but this cardioprotection is lost later in life, suggesting a role for estrogen. Although endogenous estrogen is most likely a mediator of the observed functional differences in both health and disease, the signaling mechanisms involved are complex and are not yet fully understood. To investigate how sex modulates CVD development, animal models are essential tools and should be useful in the development of therapeutics. This review will focus on describing the cardiovascular sexual dimorphisms that exist both physiologically and in common animal models of CVD.
在美国，每年近三分之一的死亡是由心血管疾病（CVD）导致的。过去，人们认为CVD主要影响男性，这使得女性和雌性动物被排除在临床研究和临床前研究之外。鉴于CVD中的性别二态性，有必要研究人类以及用于模拟CVD的动物的基线心脏差异。在人类中，从动作电位持续时间、线粒体能量代谢到心肌细胞和全心收缩功能，心血管生理学的各个层面都存在明显的性别差异。生物性别是CVD发展的一个重要调节因素，年轻女性通常受到保护，但这种心脏保护作用在生命后期会丧失，这表明雌激素发挥了作用。尽管内源性雌激素很可能是健康和疾病中观察到的功能差异的介质，但所涉及的信号机制很复杂，尚未完全了解。为了研究性别如何调节CVD的发展，动物模型是必不可少的工具，并且应该有助于治疗方法的开发。本综述将重点描述生理上以及常见的CVD动物模型中存在的心血管性别二态性。
