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Dr Yvonne Dempsie

2014 pump priming award recipient

Dr Yvonne Dempsie, Glasgow Caledonian University

Pulmonary arterial hypertension (PAH) is a terminal disease, associated with both constriction and thickening of the pulmonary arteries. This eventually leads to failure of the right heart. Current vasodilator therapies prolong life rather than curing disease, therefore novel therapeutic approaches are urgently needed.

Cellular communication is thought to be critical to both the pulmonary vascular remodelling process and to pulmonary arterial constriction. Connexins are a family of transmembrane proteins which form gap junction intercellular communication channels and permit the exchange of small regulatory molecules and ions between neighbouring cells.

Recent in vitro evidence has shown that connexions, particularly connexin 43 (Cx43), may play a role in both constriction and remodelling of the pulmonary vasculature. For example, Cx43 has been shown to mediate serotonin- signalling between pulmonary artery endothelial and smooth muscle cells (PASMCs) in vitro. Serotonin is known to mediate both proliferation and contraction of PASMCs. In line with this, pharmacological inhibition of Cx43 can attenuate contraction of isolated rat pulmonary arteries. However, the role of Cx43 in the development of PAH in vivo remains to be investigated.

We propose to study development of PAH in mice globally heterozygous for Cx43 (Cx43+/- mice) using the recently developed chronic hypoxic +SU5416 model. This model exhibits a vascular pathology consistent with human PAH.