Oestrogen receptor alpha in pulmonary hypertension.

Aims: Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression.

Sex-dependent influence of endogenous estrogen in pulmonary hypertension.

Rationale: The incidence of pulmonary arterial hypertension is greater in women, suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males, exogenously administered estrogen can protect against pulmonary hypertension (PH). However, in models that display female susceptibility, estrogens may play a causative role.

Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile.

Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.

Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension.

Aims: Pulmonary arterial hypertension (PAH) occurs more frequently in women than men. Oestrogen and the oestrogen-metabolising enzyme cytochrome P450 1B1 (CYP1B1) play a role in the development of PAH. Anorectic drugs such as dexfenfluramine (Dfen) have been associated with the development of PAH.

The serotonin transporter, gender, and 17β oestradiol in the development of pulmonary arterial hypertension.

Aims: Idiopathic and familial forms of pulmonary arterial hypertension (PAH) predominantly affect females through an unknown mechanism. Activity of the serotonin transporter (SERT) may modulate the development of PAH, and mice overexpressing SERT (SERT+ mice) develop PAH and severe hypoxia-induced PAH. In the central nervous system, oestrogens influence activity of the serotonin system.