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Dr Kirsty Mair

2013 pump priming award recipient

Dr Kirsty Mair, Durham University

The role of oestrogen and sphingosine kinase in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterised by severe pulmonary arterial remodelling and occlusive pulmonary vascular lesions, leading to right heart failure. Recent epidemiological studies report the incidence of the disease is far greater in females than males (~4:1). Oestrogen has been implicated in the pathogenesis of the disease however the mechanisms underlying this require further investigation.

As pulmonary hypertension is a hyper-proliferative disorder associated with aberrant proliferation of cells within the pulmonary artery many parallels can be drawn with cancer. Several studies investigating the mechanisms underlying oestrogen-sensitive breast cancer have linked oestrogen to the activation of sphingosine kinase (SK), resulting in the production of the sphingolipid sphingosine-1-phopshate (S1P) which is a well documented mitogen.

Using novel animal models of PAH and the selective oestrogen-receptor modulator tamoxifen, the hypothesis that “oestrogen via the activation of SK mediates the progression of PAH” will be investigated.