Sex, Gender, and Sex Hormones in Pulmonary Hypertension and Right Ventricular Failure

被引:127
作者
Hester, James [1 ]
Ventetuolo, Corey [2 ,3 ]
Lahm, Tim [1 ,4 ,5 ]
机构
[1] Indiana Univ Sch Med, Dept Med, Div Pulm Allergy Crit Care Occupat & Sleep Med, Indianapolis, IN 46202 USA
[2] Brown Univ, Dept Med, Alpert Med Sch, Div Pulm Crit Care & Sleep Med, Providence, RI 02912 USA
[3] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA
[4] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA
[5] Richard L Roudebush Vet Affairs Med Ctr, 1481 W 10th St, Indianapolis, IN 46202 USA
关键词
ESTROGEN-RECEPTOR-ALPHA; NITRIC-OXIDE SYNTHASE; CATECHOL-O-METHYLTRANSFERASE; CONGENITAL HEART-DISEASE; SMOOTH-MUSCLE-CELLS; ENDOTHELIAL PROGENITOR CELLS; MEMBRANE ANDROGEN RECEPTOR; ARTERIAL-HYPERTENSION; DEHYDROEPIANDROSTERONE-SULFATE; SYSTEMIC-SCLEROSIS;
D O I
10.1002/cphy.c190011
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Pulmonary hypertension (PH) encompasses a syndrome of diseases that are characterized by elevated pulmonary artery pressure and pulmonary vascular remodeling and that frequently lead to right ventricular (RV) failure and death. Several types of PH exhibit sexually dimorphic features in disease penetrance, presentation, and progression. Most sexually dimorphic features in PH have been described in pulmonary arterial hypertension (PAH), a devastating and progressive pulmonary vasculopathy with a 3-year survival rate <60%. While patient registries show that women are more susceptible to development of PAH, female PAH patients display better RV function and increased survival compared to their male counterparts, a phenomenon referred to as the "estrogen paradox" or "estrogen puzzle" of PAH. Recent advances in the field have demonstrated that multiple sex hormones, receptors, and metabolites play a role in the estrogen puzzle and that the effects of hormone signaling may be time and compartment specific. While the underlying physiological mechanisms are complex, unraveling the estrogen puzzle may reveal novel therapeutic strategies to treat and reverse the effects of PAH/PH. In this article, we (i) review PH classification and pathophysiology; (ii) discuss sex/gender differences observed in patients and animal models; (iii) review sex hormone synthesis and metabolism; (iv) review in detail the scientific literature of sex hormone signaling in PAH/PH, particularly estrogen-, testosterone-, progesterone, and dehydroepiandrosterone (DHEA)-mediated effects in the pulmonary vasculature and RV; (v) discuss hormone-independent variables contributing to sexually dimorphic disease presentation; and (vi) identify knowledge gaps and pathways forward. (c) 2020 American Physiological Society.
引用
收藏
页码:125 / 170
页数:46
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