Liu Aiping, Hacker Timothy, Eickhoff Jens C, Chesler Naomi C
Department of Biomedical Engineering, 2146 Engineering Centers Building, 1550 Engineering Drive, Madison, WI, 53706, USA.
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Ann Biomed Eng. 2017 Mar;45(3):632-643. doi: 10.1007/s10439-016-1716-1. Epub 2016 Aug 24.
Pulmonary arterial hypertension (PAH) is caused by extensive pulmonary vascular remodeling that increases right ventricular (RV) afterload and leads to RV failure. PAH predominantly affects women; paradoxically, female PAH patients have better outcomes than men. The roles of estrogen in PAH remain controversial, which is referred to as "the estrogen paradox". Here, we sought to determine the role of estrogen in pulsatile pulmonary arterial hemodynamic changes and its impact on RV functional adaption to PAH. Female mice were ovariectomized and replenished with estrogen or placebo. PAH was induced with SU5416 and chronic hypoxia. In vivo hemodynamic measurements showed that (1) estrogen prevented loss of pulmonary vascular compliance with limited effects on the increase of pulmonary vascular resistance in PAH; (2) estrogen attenuated increases in wave reflections in PAH and limited its adverse effects on PA systolic and pulse pressures; and (3) estrogen maintained the total hydraulic power and preserved transpulmonary vascular efficiency in PAH. This study demonstrates that estrogen preserves pulmonary vascular compliance independent of pulmonary vascular resistance, which provides a mechanical mechanism for ability of estrogen to delay disease progression without preventing onset. The estrogenic protection of pulsatile pulmonary hemodynamics underscores the therapeutic potential of estrogen in PAH.
肺动脉高压（PAH）是由广泛的肺血管重塑引起的，这种重塑会增加右心室（RV）后负荷并导致右心室衰竭。PAH主要影响女性；矛盾的是，女性PAH患者的预后比男性更好。雌激素在PAH中的作用仍存在争议，这被称为“雌激素悖论”。在此，我们试图确定雌激素在搏动性肺动脉血流动力学变化中的作用及其对右心室功能适应PAH的影响。对雌性小鼠进行卵巢切除术，并用雌激素或安慰剂进行补充。用SU5416和慢性低氧诱导PAH。体内血流动力学测量结果显示：（1）雌激素可防止肺血管顺应性丧失，对PAH中肺血管阻力增加的影响有限；（2）雌激素可减轻PAH中波反射的增加，并限制其对肺动脉收缩压和脉压的不利影响；（3）雌激素可维持总水力功率，并在PAH中保持跨肺血管效率。本研究表明，雌激素可独立于肺血管阻力维持肺血管顺应性，这为雌激素延缓疾病进展而不阻止疾病发生的能力提供了一种机械机制。雌激素对搏动性肺血流动力学的保护作用突出了雌激素在PAH中的治疗潜力。
