Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, Jinan, China;
Am J Physiol Heart Circ Physiol. 2014 Mar 1;306(5):H628-40. doi: 10.1152/ajpheart.00859.2013. Epub 2014 Jan 10.
The prevalence of left ventricular diastolic dysfunction (LVDD) sharply increases in women after menopause and may lead to heart failure. While evidence suggests that estrogens protect the premenopausal heart from hypertension and ventricular remodeling, the specific mechanisms involved remain elusive. Moreover, whether there is a protective role of estrogens against cardiovascular disease, and specifically LVDD, continues to be controversial. Clinical and basic science have implicated activation of the renin-angiotensin-aldosterone system (RAAS), linked to the loss of ovarian estrogens, in the pathogenesis of postmenopausal diastolic dysfunction. As a consequence of increased tissue ANG II and low estrogen, a maladaptive nitric oxide synthase (NOS) system produces ROS that contribute to female sex-specific hypertensive heart disease. Recent insights from rodent models that mimic the cardiac phenotype of an estrogen-insufficient or -deficient woman (e.g., premature ovarian failure or postmenopausal), including the ovariectomized congenic mRen2.Lewis female rat, provide evidence showing that estrogen modulates the tissue RAAS and NOS system and related intracellular signaling pathways, in part via the membrane G protein-coupled receptor 30 (GPR30; also called G protein-coupled estrogen receptor 1). Complementing the cardiovascular research in this field, the echocardiographic correlates of LVDD as well as inherent limitations to its use in preclinical rodent studies will be briefly presented. Understanding the roles of estrogen and GPR30, their interactions with the local RAAS and NOS system, and the relationship of each of these to LVDD is necessary to identify new therapeutic targets and alternative treatments for diastolic heart failure that achieve the cardiovascular benefits of estrogen replacement without its side effects and contraindications.
左心室舒张功能障碍 (LVDD) 在绝经后女性中的患病率急剧上升，可能导致心力衰竭。虽然有证据表明雌激素可保护绝经前女性的心脏免受高血压和心室重构的影响，但具体的相关机制仍不清楚。此外，雌激素是否对心血管疾病，特别是 LVDD 具有保护作用，仍然存在争议。临床和基础科学研究表明，与卵巢雌激素丧失相关的肾素-血管紧张素-醛固酮系统 (RAAS) 的激活在绝经后舒张功能障碍的发病机制中起作用。由于组织中 ANG II 增加和雌激素水平降低，适应性不良的一氧化氮合酶 (NOS) 系统产生 ROS，导致女性特有的高血压性心脏病。最近从模拟雌激素不足或缺乏女性（例如，卵巢早衰或绝经后）心脏表型的啮齿动物模型中获得的新见解，包括去卵巢同源 mRen2.Lewis 雌性大鼠，提供了证据表明雌激素调节组织 RAAS 和 NOS 系统及其相关的细胞内信号通路，部分通过膜 G 蛋白偶联受体 30 (GPR30；也称为 G 蛋白偶联雌激素受体 1)。补充该领域的心血管研究，将简要介绍 LVDD 的超声心动图相关性以及其在临床前啮齿动物研究中的固有局限性。了解雌激素和 GPR30 的作用、它们与局部 RAAS 和 NOS 系统的相互作用以及它们各自与 LVDD 的关系，对于确定新的治疗靶点和替代治疗方法以治疗舒张性心力衰竭以实现雌激素替代的心血管益处而没有其副作用和禁忌症是必要的。
