The influence of gender on the development of pulmonary arterial hypertension

Abstract

New Findings: • What is the Topic of this review? Pulmonary arterial hypertension (PAH) in its idiopathic and familial forms occurs more frequently in females than in males (>2:1 incidence ratio). Experimentally, however, female gender and oestrogens can both protect against and exacerbate PAH. This review will discuss our current understanding of the influence of sex hormones on the development of PAH. • What advances does it highlight? Findings from recently described female gender-specific murine models of PAH will be highlighted. Specifically, the role of oestrogen metabolism and the oestrogen-metabolizing enzyme CYP1B1 in the development of PAH are discussed. Recent evidence suggesting that sex hormones have direct effects on the right ventricle is also discussed. Pulmonary arterial hypertension (PAH) is a progressive disease in which increased pulmonary arterial pressure and remodelling eventually lead to right heart failure and death. Idiopathic and familial PAH occur far more frequently in women than in men. Historically, investigations into this gender bias have been impeded because female gender and oestrogens paradoxically protect against PAH in commonly used rodent models. However, recent descriptions of female gender-specific murine models of PAH have led to an increased understanding of the role of oestrogens in disease development. Specifically, oestrogen metabolism has been highlighted as playing an important role in disease development, and the oestrogen-metabolizing enzyme CYP1B1 may represent a novel therapeutic target. In addition, emerging evidence suggests that sex hormones may have direct effects on the right ventricle independent of haemodynamic effects. This review discusses our current understanding of the role of sex hormones in the development of PAH. © 2013 The Physiological Society.